bims-axbals 2026-07-12 papers

bims-axbals

Biomed News

on Axonal biology and ALS

Issue of 2026–07–12
27 papers selected by
TJ Krzystek

Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.
Patient-derived forebrain cortical organoids reveal biphasic tau-MAP6-microtubule axis dysfunction in tauopathy.
Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.
Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.
Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTD.
Dysregulated neuronal mRNA transport and translation in FTD/ALS.
Metabolic Kinases as Regulators of Inter-Organelle Communication in Aging and Age-Related Diseases.
CDKN1A protects medium spiny neurons from Huntington's disease pathology.
Elevation of the mechanically-sensitive e protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons.
Human iPSC-Derived Spinal Neurons Carrying the ALS FUS (P525L) Mutation Exhibit Lower Response to Inhibitory Neurotransmitters.
Clinical Relevant Immunosuppressive Drugs Differentially Modulate Axonal Outgrowth from Human Stem Cell-Derived Neurons.
C9orf72-associated poly-GR in skeletal muscle leads to neuromuscular junction deficits and muscle atrophy.
Activity-dependent lipid droplet biogenesis and turnover regulate synaptic integrity.
KCTD3 deficiency disrupts axon initial segment organization and neurite outgrowth in a neurodevelopmental disorder mouse model.
Huntington's disease in the era of somatic instability, biomarkers, and targeted therapies: A narrative review.
R1398 is the GTP-𝛾-phosphate sensor that drives the ROC G-domain switching mechanism unique to Parkinson's disease-associated LRRK2.
The Golgi as a Microtubule Organiser in Neurons.
Annexin A11 and TDP-43: core players in neurodegeneration.
Neuroprotective potential of resveratrol in Parkinson, Huntington, amyotrophic lateral sclerosis, and multiple sclerosis: a comprehensive review.
ER-mitochondria tether ML1 coordinates peripheral fission and wholesale mitophagy for plant adaptation to carbon starvation.
CLASP2 promotes repair of kinesin-1 damage to the microtubule lattice.
Dendritic morphology and synaptic nonlinearities enhance functional complexity in human cortical neurons.
Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.
Investigating the effect of progressive truncations at the ALS-linked protein TDP-43 RRM2 on its aggregation mechanism.
CAST controls presynaptic sequestration of Rab6 in neurons.
iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntington's disease.
Whole-Mount Immunostaining of Tyrosine Hydroxylase for Dopaminergic Neuron Analysis in Zebrafish Larvae.

Cell Rep. 2026 Jul 07. pii: S2211-1247(26)00750-3. [Epub ahead of print]45(7): 117672

Striatal neuron dysfunction in C9ORF72-FTD/ALS is driven by AIS and potassium channel dysregulation.

Iris-Stefania Pasniceanu, Manpreet S Atwal, Cleide Dos Santos Souza, Tobias Moll, Marianne King, Connie Treanor, Daniel Cabezas de la Fuente, Ryan J H West, Laura Ferraiuolo, Matthew R Livesey.

  Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) form a neurodegenerative spectrum characterized by progressive cognitive, behavioral, and motor decline, yet the contribution of the striatum to disease pathophysiology remains poorly understood. Here, we generate inhibitory striatal medium spiny neurons (MSNs) from human induced pluripotent stem cells carrying the C9ORF72 repeat expansion, the most common genetic cause of FTD/ALS, and compare them with isogenic-corrected, control, and patient-derived motor neurons. Using whole-cell electrophysiology, pharmacological manipulation, and high-resolution imaging, we identify a vulnerability of C9ORF72 MSNs to develop intrinsic hypoexcitability with linked synaptic dysfunction. These abnormalities are associated with axon initial segment shortening and altered voltage-gated potassium channel function relative to control and isogenic-corrected neurons. Pharmacological modulation partially restores action potential waveform properties, indicating that key electrophysiological abnormalities are reversible. These findings identify the striatum as a critical site of dysfunction in FTD/ALS and highlight striatal excitability as a potential therapeutic target.

Keywords:  ALS; C9ORF72; CP: neuroscience; FTD; electrophysiology; excitability; inhibitory; neuron; striatal; synaptic

DOI:  https://doi.org/10.1016/j.celrep.2026.117672
Alzheimers Dement. 2026 Jul;22(7): e71565

Patient-derived forebrain cortical organoids reveal biphasic tau-MAP6-microtubule axis dysfunction in tauopathy.

Xiaohuan Sun, Skandha Ramakrishnan, Victor C Ogbolu, Nicholas M Kanaan, Celeste M Karch, Peter W Baas, Liang Qiang.

   INTRODUCTION: In frontotemporal dementia (FTD), tau detaches from axonal microtubules and forms pathological aggregates. Rather than stabilizing microtubules, tau promotes labile microtubule domains, redefining its role in neurodegeneration and underscoring the need for human models that capture temporal disease progression.
METHODS: Human induced pluripotent stem cells carrying MAPTWT/P301L, MAPTWT/P301S, or MAPTWT/R406W mutations and isogenic controls were differentiated into forebrain cortical organoids (1 to 8 months). Tau isoforms, microtubule dynamics, MAP6 regulation, neuronal activity, tau mRNA stability, and tau pathology were analyzed using biochemical, imaging, and electrophysiological approaches, some of which were benchmarked to postmortem behavorial variant FTD cortex.
RESULTS: Early-phase tau mutant organoids showed elevated tau, hyperdynamic microtubules, and neuronal hyperexcitability, partially reversible by tau reduction. Late-phase organoids exhibited insoluble tau accumulation, microtubule hyperstability, and neurodegeneration and reactive astrocytes, accompanied by opposing, phase-dependent MAP6 changes.
DISCUSSION: This work reveals a biphasic tau-MAP6-microtubule mechanism driving tauopathy and establishes these organoids as a platform for phase-specific therapy.

Keywords:  MAP6; cortical organoids; microtubule; tau; tauopathy

DOI:  https://doi.org/10.1002/alz.71565
Nat Rev Neurosci. 2026 Jul 06.

Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.

Benedetta Frizzi, Adriana Margarida Barbosa Correia, Irene Faravelli, Ludo Van Den Bosch, Stefania Corti.

Motor neuron diseases (MNDs) are caused by the progressive loss of motor neurons and eventually lead to paralysis and death. Once viewed as primarily neurocentric, MNDs are now recognized to be driven by intertwined cell-autonomous and non-cell-autonomous mechanisms. Dissecting these interactions is essential for developing effective therapies. Here, we describe induced pluripotent stem cell-derived 3D models that can be used to capture distinct aspects of MND pathology. We show that spinal cord organoids can be used to investigate cell-autonomous mechanisms and motor neuron-glia interactions (with axially elongated spinal cord organoids being particularly useful to study developmental vulnerability) as well as in 3D muscle and combined neuromuscular models to dissect muscle pathology and neuromuscular junction dismantling. In parallel, we discuss advances in bioengineering, machine learning and human trunk-like models, which together can begin to reproduce the coordinated co-development and spatial organization of the multiple tissues affected in MNDs. We discuss how these systems have advanced our understanding of disease mechanisms and highlight opportunities for drug repurposing. Finally, we propose a mechanism-informed and phenotype-informed framework to guide 3D model selection for future research and to prioritize promising avenues for therapeutic development.

DOI: https://doi.org/10.1038/s41583-026-01057-x
Brain Commun. 2026 ;8(4): fcag241

Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.

Stefania Corti, Claudia Alberti, Linda Ottoboni, Giulia Magni, Delia Gagliardi, Filippo Marcotti, Simona Zanotti, Maurizio Moggio, Giacomo Pietro Comi.

  Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by accumulation of the 43-kDa TAR DNA-binding protein (TDP-43). This neuropathological signature has been well documented within the CNS; however, recent findings indicate that the phosphorylated TDP-43 additionally deposits in peripheral tissues, including skeletal muscle and intramuscular nerves. These data warrant a change of view from a neurocentric perspective of amyotrophic lateral sclerosis pathogenesis towards a broader concept of TDP-43 proteinopathy extending both within and beyond the nervous system. In this review, we focus on current evidence supporting the presence of TDP-43 pathology in amyotrophic lateral sclerosis skeletal muscle, examining its topographic distribution, molecular characteristics and associations with intramuscular nerve bundles. We also discuss the susceptibility of intrinsic muscle cells, disrupted axonal transport and impairment in protein quality control. Phosphorylated TDP-43 pathology in muscle biopsies from amyotrophic lateral sclerosis patients has emerged as a promising tool in the early diagnosis of the disease. Moreover, we discuss the relevance of these findings to amyotrophic lateral sclerosis pathogenesis and potential therapeutic implications.

Keywords:  TDP-43; amyotrophic lateral sclerosis; diagnostic biomarker; peripheral proteinopathy; skeletal muscle

DOI:  https://doi.org/10.1093/braincomms/fcag241
bioRxiv. 2026 Jul 01. pii: 2026.01.24.701325. [Epub ahead of print]

Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTD.

Emma Dixon, Fereshteh Azimian, Angelina Joby Chacko, Rodney Tatum, Christi Boykin, Yan-Hua Chen, Qun Lu.

The hexanucleotide repeat expansion in C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). The C9orf72 protein forms a complex with SMCR8 and WDR41 (CSW), which functions as a GTPase-activating protein (GAP) regulating ARF1 and RAB small GTPases. While these findings implicated ARF1-GAP dysregulation in ALS/FTD and supported ARF1 suppression as potential intervention, small molecules that modulate ARF1-CSW interactions are lacking. In this study, we demonstrated upregulation of tyrosine-phosphorylated (Tyr-782) ASAP1 (also known as AMAP1, DDEF1, or Centaurin β4), an ARF-GAP, in human motor cortex of both sporadic ALS and ALS with C9orf72 mutations. Ectopic C9orf72 expression partially mimicked the effects of a known ARF1 inhibitor brefeldin A to disperse Golgi apparatus. Computer-aided rational drug design with high-throughput in-silico screening identified MCULE-5095997944 (Named as SCC944) as a ARF1-CSW modulator. SCC944 binds directly to ARF1 and reduced GTP-bound ARF1 levels upon ARF1 activation. SCC944 demonstrated brefeldin A-like ARF1-dependent alteration of organelle organization including Golgi, microtubules, and mitochondria, but also a protein trafficking pattern that is distinct from brefeldin A mechanism. These studies identified the first small molecule targeting ARF1-CSW interaction and further support ARF1 modulation as a potential therapeutic approach for ALS/FTD.

DOI: https://doi.org/10.64898/2026.01.24.701325
NPJ Dement. 2026 ;2(1): 56

Dysregulated neuronal mRNA transport and translation in FTD/ALS.

Emma J Craig, Veronica H Ryan.

  Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal, co-occurring neurodegenerative disorders. Dysregulation of mRNA metabolism, transport, and local translation is a significant mechanism contributing to FTD/ALS. Here, we review the processes of neuronal RNA transport and translation, their disruption in FTD/ALS, and mechanistic interplay between the two. Finally, we discuss current progress targeting transport and translation defects and identify potential future directions for therapeutic development.

Keywords:  Neurology; Neuroscience

DOI:  https://doi.org/10.1038/s44400-026-00116-5
Aging Cell. 2026 Jul;25(7): e70624

Metabolic Kinases as Regulators of Inter-Organelle Communication in Aging and Age-Related Diseases.

Md Riad Chowdhury, Jae-Han Jeon, Dipanjan Chanda.

  Cellular aging is accompanied by progressive alterations in metabolic homeostasis, stress adaptation, and organelle function. Increasing evidence suggests that functional coordination among membrane-bound organelles, including mitochondria, the endoplasmic reticulum (ER), lysosomes, peroxisomes, and the Golgi apparatus, contributes to cellular homeostasis during aging. However, the mechanisms linking kinase signaling to specific inter-organelle contact sites or communication pathways remain incompletely defined. In this review, we discuss current evidence linking major metabolic and stress-responsive kinases, including AMPK, pyruvate dehydrogenase kinases (PDKs), mTOR, AKT, and PERK, to organelle coordination in aging and age-related diseases. These kinases regulate mitochondrial dynamics, metabolic flux, calcium and lipid handling, autophagy, lysosomal function, proteostasis, and vesicular trafficking. In some contexts, kinase signaling intersects with defined organelle interfaces, such as mitochondria-associated ER membranes, whereas in many cases the effects on inter-organelle communication are indirect or inferred from broader changes in organelle function. We further discuss how kinase dysregulation may contribute to age-associated defects in mitochondria-ER, mitochondria-lysosome, mitochondria-peroxisome, and ER-Golgi coordination in neurodegeneration, cardiometabolic disease, cellular senescence, and inflammaging. By distinguishing direct contact-site regulation from indirect functional coordination, this review highlights kinase-regulated organelle communication as an emerging, but still incompletely resolved, framework for understanding cellular decline during aging.

Keywords:  age‐related diseases; aging; inter‐organelle communication; metabolic kinases; mitochondrial quality control

DOI:  https://doi.org/10.1111/acel.70624
Neurobiol Dis. 2026 Jul 06. pii: S0969-9961(26)00267-6. [Epub ahead of print]227 107522

CDKN1A protects medium spiny neurons from Huntington's disease pathology.

Seong Won Lee, Trinity J Upshaw, Diandra J Bailey, Shin-Ae Lee, Jihyun Kim, Paarthivi Joshi, Genevieve Evelynne Smith, Samuel Swinford, Young Mi Oh.

  Huntington's disease (HD) arises from abnormal expansion of CAG trinucleotide repeats within the HTT gene, leading to mutant huntingtin (mHTT) aggregation, progressive loss of striatal medium spiny neurons (MSNs), and progressive neurodegeneration. While the genetic cause is established, the mechanisms that confer selective MSN vulnerability, particularly those linked to aging, remain unclear. We employed a combination of miR-9/9*-124-driven reprogramming and MSN-specific transcription factors to generate patient-derived MSNs from fibroblasts of symptomatic HD patients (HD-MSNs), pre-symptomatic mutation carriers (pre-HD-MSNs), and healthy controls, preserving donor age signatures. Multi-omics analysis integrating RNA-seq and ATAC-seq revealed reduced CDKN1A expression and promoter accessibility in HD-MSNs compared with pre-HD-MSNs. Overexpression of CDKN1A in HD-MSNs alleviated HD pathologies, including DNA double-strand breaks, oxidative DNA damage, and mHTT aggregates, while improving neuronal survival and autophagy-associated activity. Conversely, knockdown of CDKN1A in pre-HD-MSNs elicited opposite effects, revealing a CDKN1A-dependent survival mechanism in HD. Together, these findings suggest that reduced CDKN1A expression may contribute to HD-associated MSN vulnerability and is associated with altered DNA damage responses and autophagy-related processes in HD-MSNs. Our study identifies CDKN1A as a potential modulator of neuronal resilience in HD.

Keywords:  CDKN1A; Directly reprogrammed neurons; Huntington's disease; Medium spiny neurons; Neurodegeneration

DOI:  https://doi.org/10.1016/j.nbd.2026.107522
Nucleus. 2026 Dec;17(1): 2697135

Elevation of the mechanically-sensitive e protein emerin links nuclear mechanotransduction to tau-induced cytoskeletal remodeling in neurons.

Claira Sohn, Sammy Pardo, Dana Molleur, Satvik R Paduri, Morgan Lambert, Zachary Uttke, Erich J Sohn, Morgan G Thomas, Susan T Weintraub, Bess Frost.

  Neurodegenerative tauopathies, including Alzheimer's disease, are neuropathologically defined by pathological tau deposition. While tau drives neurotoxicity by disrupting cytoskeletal, nucleoskeletal, and genomic architecture, cellular mechanisms mediating tau-induced dysfunction of the cytoskeleton and nucleoskeleton are incompletely understood. Here, we identify proteins with differing abundance in a cellular tauopathy model, iTau. Building upon previous findings that pathogenic tau reduces nuclear tension, we find elevated levels of emerin, a central regulator of nuclear mechanotransduction, in iTau neurons and tau mutant iPSC-derived neurons. Neuronal emerin overexpression drives neurotoxicity, increases filamentous actin (F-actin), and induces nuclear invagination, mimicking cellular phenotypes of tauopathy. Alterations in emerin binding partners reflect its cytosolic relocalization in iTau neurons, suggesting that pathogenic tau may impact nuclear mechanotransduction by altering emerin levels and localization. Overall, we identify emerin as a potential mediator of cytoskeletal and nucleoskeletal remodeling in tauopathy and provide a foundation for future studies of emerin function in neurons.

Keywords:  Alzheimer’s disease; Mechanotransduction; actin; cytoskeleton; emerin; nucleus; tau; tauopathy

DOI:  https://doi.org/10.1080/19491034.2026.2697135
Cell Mol Neurobiol. 2026 Jul 10.

Human iPSC-Derived Spinal Neurons Carrying the ALS FUS (P525L) Mutation Exhibit Lower Response to Inhibitory Neurotransmitters.

Tiziano D'Andrea, Maria Cristina Benedetti, Michela Mochi, Valeria De Turris, Alessandro Rosa, Sergio Fucile.

  Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder characterized by motoneurons degeneration. Functional studies have linked ALS to hyperexcitability and excitotoxicity, but the cause of the disease is unknown, though familial ALS cases are linked to pathogenic variants in several genes, including SOD1, TARDBP and FUS. Here we focused on the effect of the severe FUS (P525L) mutation on the functional properties of human spinal neurons derived from induced pluripotent stem cells (hiPSCs). This mutation delayed functional maturation, as revealed by the observation that mutated neurons showed alterations of membrane potential, reduced spontaneous synaptic activity, and altered action potentials at early differentiation stages. FUS (P525L) mutation was associated with a significant alteration of inhibitory signalling transmission: mutated neurons showed a significantly lower current response to GABA and glycine compared to control isogenic WT neurons of the same age. Also, glutamatergic currents exhibited a different temporal evolution in control and mutated neurons, but at a lower extent in comparison to inhibitory neurotransmitters. The decrease in the glycine-evoked currents was confirmed by the reduction of the expression of the α1 subunit of glycine receptor, measured by immunofluorescence assay. Similar functional alterations were measured in spinal neurons differentiated form a second hiPSC line, confirming the causative role of the FUS (P525L) mutation. Our data indicate that the FUS (P525L) mutation reduces the maturation rates and the function of hiPSC-derived spinal neurons, with a strong decrease of inhibitory transmission, which may affect the excitatory/inhibitory balance, possibly predisposing to excitotoxicity and neurodegeneration.

Keywords:  Excitotoxicity; Glycinergic transmission; Inhibitory/excitatory balance; Neurodegeneration; Neurotransmission

DOI:  https://doi.org/10.1007/s10571-026-01773-z
bioRxiv. 2026 Jul 02. pii: 2026.06.29.735084. [Epub ahead of print]

Clinical Relevant Immunosuppressive Drugs Differentially Modulate Axonal Outgrowth from Human Stem Cell-Derived Neurons.

Gunnar H D Poplawski, C Weinholtz, G Woodruff, R Ahmad, W Bunner, Rodrigo Gonzales, M H Tuszynski.

Neural stem cell (NSC) transplantation is a promising strategy for repairing the injured spinal cord, but transplanted cells typically require immunosuppressive therapy to prevent rejection-even for induced pluripotent stem cell (iPSC)-derived autologous grafts. However, the effects of immunosuppressive drugs on neurite outgrowth and axonal regeneration- processes critical for neural circuit reconstruction-have not been fully characterized. In this study, we tested nine clinically relevant immunosuppressants on human iPSC-derived neurons and primary human spinal cord NSCs in vitro at concentrations approximating clinical exposure levels. The drug panel included FK-506 (tacrolimus), cyclosporine A (CsA), rapamycin, belatacept (Nulojix), etanercept (Enbrel), mycophenolate mofetil (CellCept), cyclophosphamide (Cytoxan), prednisone, and azathioprine (Imuran). Neurite outgrowth was quantified via automated high-content imaging. Multiple agents, including CsA, Imuran, Nulojix, and CellCept, induced significant reductions in neurite outgrowth in a cell type- and dose-dependent manner, with CsA producing the most robust and consistent inhibition across both cell lines. In contrast, FK-506 showed no significant effect on neurite extension at clinically relevant concentrations. Consistent with the in vitro results, human neural progenitor cell grafts in a rodent spinal cord injury model exhibited significantly reduced graft-derived axon extension in the host spinal cord when hosts were treated with CsA rather than FK-506. These findings demonstrate that immunosuppressant choice can profoundly influence neural graft integration and axonal regeneration. Our study underscores the importance of preclinical evaluation of immunosuppressive regimens and suggests that selecting agents such as FK-506 over CsA may improve outcomes in future stem cell-based therapeutic trials for spinal cord injury and related disorders of the central nervous system.
Highlights: Cyclosporine A inhibits axon outgrowth in human neurons in vitroFK-506 preserves neurite extension across stem cell-derived neuron typesAxon outgrowth is reduced in vivo with CsA but not FK-506Immunosuppressant selection critically affects neural graft integrationFK-506 may be preferable to CsA for SCI cell transplantation protocols.

DOI: https://doi.org/10.64898/2026.06.29.735084
Mol Ther. 2026 Jul 09. pii: S1525-0016(26)00567-8. [Epub ahead of print]

C9orf72-associated poly-GR in skeletal muscle leads to neuromuscular junction deficits and muscle atrophy.

Xinyi Tan, Shuangshuang Sun, Yuqing Yan, Wei Li, Ning Ding, Lin Xu, Liying He, Yuhao Zhang, Wenbing Chen, Yongjun Zheng, Lei Li.

Hexanucleotide repeat expansions in C9orf72 produce dipeptide repeat (DPR) proteins that are widely expressed, including the nervous system and skeletal muscle. Among these DPRs, arginine-containing proteins, poly-GR and poly-PR are toxic in the nervous system, but whether DPRs in skeletal muscle contribute to ALS pathogenesis is unclear. Here, we show that muscle-restricted expression of poly-GR drives motor deficits in mice, including muscle atrophy and neuromuscular junction (NMJ) deficits. Poly-GR in muscle interacted with the NMJ key organizer MuSK and promoted MuSK degradation, disrupting postsynaptic structure and impairing neuromuscular transmission. Importantly, a MuSK agonist antibody (X-17) stabilized NMJs and rescued neuromuscular transmission. Moreover, poly-GR in muscle activated the integrated stress response (ISR), elevating eIF2α phosphorylation and broadly suppressing protein translation. ISR inhibition with ISRIB restored translation and MuSK protein levels, and ameliorated both muscle atrophy and NMJ deficits. These findings demonstrate that skeletal muscle actively contributes to C9orf72-ALS pathology. Targeting muscle with ISRIB offers a therapeutic strategy to preserve motor function in C9orf72-ALS.

DOI: https://doi.org/10.1016/j.ymthe.2026.07.002
bioRxiv. 2026 Jun 29. pii: 2026.06.25.734633. [Epub ahead of print]

Activity-dependent lipid droplet biogenesis and turnover regulate synaptic integrity.

Eleni Katafygiotou, Ada Squires, Anne Liang, Holden Hadfield, João A Paulo, Walid Idi, Steven P Gygi, Joongkyu Park, Jeeyun Chung.

Lipid droplets (LDs) are conserved organelles that buffer lipid storage and stress, yet their dynamics and functions in neurons remain largely unknown. Here, we report activity-dependent dynamics of neuronal LDs, visualized by a novel, genetically encoded LD reporter (termed LipiDew), in both cultured neurons and mouse motor cortex. Using LipiDew, we found that various paradigms of neuronal activation induced predominant and transient formation of LDs in neurites. Disruption of autophagic LD degradation (lipophagy) resulted in abnormal lipid accumulation in dendritic spines and shafts, promoted recruitment of synaptic scaffolding proteins to LDs, and altered intracellular calcium kinetics in neurons. In addition, mice with neuron-specific genetic impairment of lipophagy showed motor function defects. Together, these findings identify activity-dependent LD formation and lipophagic clearance in neuronal compartments as a crucial regulatory mechanism of synaptic integrity and neuronal function.

DOI: https://doi.org/10.64898/2026.06.25.734633
Commun Biol. 2026 Jul 07.

KCTD3 deficiency disrupts axon initial segment organization and neurite outgrowth in a neurodevelopmental disorder mouse model.

Yeonsoo Oh, Youngha Lee, Hoyong Jin, Marcello Scala, Valeria Capra, Annalaura Torella, Vincenzo Nigro, Bertrand Isidor, Frédéric Tran Mau-Them, René G Feichtinger, Johannes A Mayr, Saskia B Wortmann, Hyeyoon Kim, Dohyun Han, Jin Sook Lee, Jong-Hee Chae, Murim Choi, Yongcheol Cho.

Pathogenic variants in human KCTD3 are associated with severe neurodevelopmental disorders characterized by early-onset seizures, developmental delay, hypotonia, and cerebellar hypoplasia, but the underlying mechanisms remain unclear. Here we show that KCTD3 regulates neuronal structural organization through DAAM1, a protein involved in actin cytoskeleton assembly. In Kctd3-deficient neurons, DAAM1 protein levels are reduced, the axon initial segment is abnormally organized, and neurite growth and growth cone morphology are impaired. These defects are rescued by DAAM1 overexpression. Systemic Kctd3 depletion also disrupts axon initial segment organization and motor axon innervation at neuromuscular junctions, leading to motor dysfunction and growth impairment in mice. These findings identify a KCTD3-DAAM1 pathway required for neuronal structural development and provide a framework for understanding how KCTD3 deficiency contributes to neurodevelopmental disorders.

DOI: https://doi.org/10.1038/s42003-026-10584-3
Rev Invest Clin. 2026 Jul 07. pii: S0034-8376(26)00014-8. [Epub ahead of print]78(4): 100047

Huntington's disease in the era of somatic instability, biomarkers, and targeted therapies: A narrative review.

Amin Cervantes-Arriaga, Ashley Xanat Beltrán-Torres, Diego Romero-García, Mayela Rodríguez-Violante.

  Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT), resulting in mutant huntingtin (mHTT) with toxic gain-of-function and partial loss of normal huntingtin function. This narrative review summarizes recent advances in genetics, pathophysiology, clinical features, diagnostic assessment, biomarkers, and therapeutic development. Genetic testing demonstrating an expanded HTT CAG repeat is the definitive diagnostic test and should be interpreted with genetic counseling and attention to allele categories. Pathophysiologically, HD involves CAG instability, age-dependent somatic expansion in vulnerable neurons, transcriptional dysregulation, proteostasis failure, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, leading primarily to degeneration of striatal medium spiny neurons and later cortical involvement. Clinically, HD can begin from juvenile to late-adult life and manifests with motor, cognitive, psychiatric, and behavioral symptoms that evolve from premanifest biological change to functional decline. Current clinical care relies on symptom-directed treatment, whereas quantitative neuroimaging, cerebrospinal fluid biomarkers are mainly used for research and trial enrichment. Symptomatic management includes vesicular monoamine transporter type 2 inhibitors, antipsychotics, rehabilitation, nutritional support, and multidisciplinary care. Emerging disease-modifying approaches include HTT-lowering, somatic expansion inhibition, and gene-based therapies, but efficacy depends on target selectivity, timing, delivery route, dose, and patient selection.

Keywords:  Antisense oligonucleotide; CAG repeat; Disease-modifying therapy; Huntingtin; Huntington's disease; Neurofilament light; Somatic instability

DOI:  https://doi.org/10.1016/j.ric.2026.100047
Res Sq. 2026 Jul 01. pii: rs.3.rs-10121216. [Epub ahead of print]

R1398 is the GTP-𝛾-phosphate sensor that drives the ROC G-domain switching mechanism unique to Parkinson's disease-associated LRRK2.

Quyen Hoang, Yangshin Park, Chunxiang Wu, Rajnesh Yadav, Kayla Tennessen, Neo Hoang, Cardea Hoang, Xylena Reed, Xiaorong Huang, Mark Cookson, R Nichols, Jingling Liao.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD). Strategies that directly inhibit the LRRK2 kinase active site have not demonstrated disease-modifying efficacy in recent clinical testing. A naturally occurring protective variant, R1398H, provides an alternative route for understanding how reduced disease risk may be achieved by tuning the regulatory GTPase domain rather than the kinase domain itself. Here, we combine structural, computational, biochemical, and cell-based analyses to define how R1398H alters the Ras of complex proteins (ROC) G domain of LRRK2. Purified ROC carrying R1398H is folded but resolves as a stable homodimer corresponding to the GDP-bound off state previously defined for wild-type ROC. A 2.0 Å crystal structure shows unambiguous density for H1398 and reveals close superposition with the GDP-bound wild-type ROC dimer. Molecular dynamics modeling predicts that R1398 engages the 𝛾-phosphate of GTP to stabilize switch-region interactions required for activation, whereas histidine at this position weakens 𝛾-phosphate sensing. Consistent with this model, R1398H reduces GTP hydrolysis, selectively weakens GTP-state stabilization while preserving GDP binding, and decreases Rab29-dependent trans-Golgi recruitment of full-length LRRK2. These findings identify R1398 as a 𝛾-phosphate sensor that couples nucleotide chemistry to ROC conformational switching and suggest a genetics-anchored strategy for stabilizing a protective off-state conformation of LRRK2.

DOI: https://doi.org/10.21203/rs.3.rs-10121216/v1
J Neurochem. 2026 Jul;170(7): e70511

The Golgi as a Microtubule Organiser in Neurons.

Akila Yagoubat, Paul T Conduit.

  Microtubules are fundamental to neuronal architecture, providing the structural framework and transport tracks essential for polarisation, compartmentalisation and growth. While the centrosome is the canonical microtubule-organising centre (MTOC), neurons also rely on non-centrosomal MTOCs (ncMTOCs) as they mature. This review explores the emerging role of the Golgi apparatus as a key ncMTOC in both vertebrate and invertebrate neurons. We examine evidence that microtubule nucleation from the somatic Golgi supports initial polarisation and axon growth and regulates microtubule polarity. We also address the ongoing debate regarding Golgi outposts and their potential role in organising the dendritic microtubule network. By synthesising the available literature, we reconcile conflicting findings and identify gaps in our current understanding of Golgi-mediated nucleation and its role in organising the neuronal microtubule cytoskeleton.

Keywords:  Golgi; MTOCs; microtubules; neurons; polarity

DOI:  https://doi.org/10.1111/jnc.70511
Acta Neuropathol. 2026 Jul 07. pii: 4. [Epub ahead of print]152(1):

Annexin A11 and TDP-43: core players in neurodegeneration.

Courtney L Smith, John L Robinson, Edward B Lee.

  Annexin A11 (ANXA11) is a Ca2⁺-dependent phospholipid-binding protein that has recently emerged as a key player in neurodegeneration. Rare pathogenic ANXA11 variants were initially identified in cases of amyotrophic lateral sclerosis (ALS). Since then, ANXA11 has been linked to a broader spectrum of related neurodegenerative diseases. Two independent studies demonstrated that ANXA11 co-aggregates with TDP-43 in all cases of frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) type C, with cryo-EM revealing heteromeric ANXA11-TDP-43 filaments. These discoveries support the direct pathological interaction between the two proteins as an important feature of FTLD-TDP type C. We also described secondary ANXA11 pathology in related neurodegenerative diseases, including limbic-predominant age-related TDP-43 encephalopathy (LATE), and more rarely in ALS and FTLD-TDP types A and B. ANXA11 and TDP-43 co-aggregates are also a feature of a FTLD-TDP associated with primary lateral sclerosis. These advances have renewed interest in ANXA11 as a major player in ALS/FTLD pathogenesis in both genetic and sporadic neurodegenerative diseases. In this review, we summarize ANXA11 pathology across genetic and sporadic cases, highlighting its heterogeneous overlap with TDP-43 pathology. We synthesize current knowledge of ANXA11's physiological roles in phase separation, membrane repair, and RNA granule dynamics, integrating emerging evidence on how disruption of these processes may promote pathological aggregation and toxicity. Finally, we outline priorities for future research, with particular emphasis on elucidating ANXA11's mechanistic connection to TDP-43.

Keywords:  ALS; Annexin A11; FTLD-TDP; Neurodegenerative disease; TDP-43

DOI:  https://doi.org/10.1007/s00401-026-03043-0
Mol Biol Rep. 2026 Jul 04. pii: 1102. [Epub ahead of print]53(1):

Neuroprotective potential of resveratrol in Parkinson, Huntington, amyotrophic lateral sclerosis, and multiple sclerosis: a comprehensive review.

Kasra Shahsavari, Omid Yazarlu, Hananeh Ahmadnia, Mahsa Tavakolian Ardakani, Mahnaz Khanavi, Hamidreza Monsef Esfahani, Reza Abdollahzadeh, Aida Sajedi, Hossein Kazemizadeh, Maede Hasanpour.

  Resveratrol shows neuroprotective effects in preclinical studies across a number of neurodegenerative illnesses, including Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Huntington's disease (HD), and it enhances mitochondrial function through stimulation of the AMPK/SIRT1/PGC-1α pathway, thereby improving mitochondrial oxidative capacity and ATP generation. The natural polyphenol lowers α-synuclein accumulation and affects autophagy; both markers of PD. Combining nano‑resveratrol formulations with L‑DOPA has shown greater therapeutic efficacy in animal models (MPTP mouse), while co‑administration with EGCG has shown synergistic neuroprotection in vitro (SH‑SY5Y cells). These combination strategies offer potential advantages in neuroprotection and symptom alleviation while minimizing adverse drug effects. Resveratrol activates SIRT1 and AMPK signaling in preclinical models, enhancing mitochondrial biogenesis, lowering apoptosis, and restoring cellular resilience. The effectiveness of various models and dosages varies. The primary mechanism by which resveratrol promotes neuronal survival and remyelination in multiple sclerosis is through SIRT1 activation, which does not directly reduce inflammation. As innovative delivery systems, intranasal nanoparticles and exosomes produced from macrophages have shown improved CNS targeting accuracy. Resveratrol slows down neurodegeneration and improves the prognosis of HD by improving motor function and stimulating mitochondrial biogenesis in addition to activating neuroprotective ERK signaling. All of these results point to resveratrol's several pathways as a strong contender for neurodegenerative disease adjunctive treatment. The current evidence base is insufficient to support clinical use of resveratrol for any of the four diseases. Further rigorous preclinical studies (including TDP-43 models for ALS, SIRT1 knockout studies, and human-feasible dosing) and well-designed clinical trials with pharmacokinetic endpoints are required before any clinical recommendations can be made.

Keywords:  Amyotrophic Lateral Sclerosis; Huntington’s Disease; Multiple Sclerosis; Neuroprotective; Parkinson’s Disease; Resveratrol

DOI:  https://doi.org/10.1007/s11033-026-12300-0
Sci Adv. 2026 Jul 10. 12(28): eaef6631

ER-mitochondria tether ML1 coordinates peripheral fission and wholesale mitophagy for plant adaptation to carbon starvation.

Benhui Shi, Baolei Li, Songyang Wang, Xu Zhang, Yu Tang, Jun Jiang, Liting Zhai, Yang Shao, Jiaqi Sun.

Plants frequently encounter carbon starvation from extended darkness or canopy shading or in nonphotosynthetic tissues, requiring rapid mitochondrial remodeling to match reduced metabolic flux. Here, we reveal a coordinated program integrating peripheral fission-mediated damage segregation and wholesale mitophagy. Carbon starvation triggers a shift from symmetric midzone fission to asymmetric peripheral fission, generating small depolarized fragments alongside larger polarized mitochondria. Unexpectedly, damage-independent wholesale mitophagy targets medium-sized mitochondria for both burden reduction and resource mobilization while excluding small peripheral fission products. We identify mitochondria-ER (endoplasmic reticulum) linker 1 (ML1), a carbon starvation-inducible ER-mitochondria tether, as the central coordinator. At ER-mitochondria contact sites, ML1 promotes peripheral fission and recruits ATG18a (autophagy-related protein 18a) for wholesale mitophagy. Loss of ML1 impairs this coordinated remodeling, resulting in elongated mitochondria, compromised function, and hypersensitivity to carbon starvation. These findings reveal how plants achieve rapid metabolic adaptation through coordinated mitochondrial remodeling.

DOI: https://doi.org/10.1126/sciadv.aef6631
bioRxiv. 2026 Jun 30. pii: 2026.06.29.735199. [Epub ahead of print]

CLASP2 promotes repair of kinesin-1 damage to the microtubule lattice.

Jakia Jannat Keya, Rahul Riberio, Yang Yue, Elizabeth J Lawrence, Marija Zanic, Kristen J Verhey.

Microtubules are cytoskeletal polymers that play essential roles in eukaryotic cells, including structural support, cell division, and intracellular transport. During intracellular transport, kinesin motor proteins move cargo along microtubule tracks via their processive stepping. Recent studies have shown that the kinesin-1 KIF5C can damage the microtubule lattice while stepping. Microtubule damage can be repaired through incorporation of new tubulin subunits, however, excessive lattice damage results in microtubule breakage and disassembly. To identify cellular factors involved in microtubule repair, we performed an siRNA screen targeting microtubule-associated proteins (MAPs) known to regulate microtubule dynamics and stability. Based on the results, we investigated whether the end binding protein EB1 and cytoplasmic linker-associated protein 2 (CLASP2) contribute to repair of microtubule damage. To test this, we used a microtubule destruction assay in which damage was induced in microtubules gliding over surfaces coated with wild-type or mutant KIF5C proteins. Our findings suggest that CLASP2 directly facilitates microtubule repair, whereas EB1 does not. We further examined CLASP function using a microtubule repair assay and found that CLASP2 promotes repair by enhancing tubulin incorporation and reducing microtubule breakage. Together, these findings demonstrate that CLASP proteins play an important role in repairing and protecting against lattice damage caused by kinesin-1 motor activity. Our results further suggest that MAPs can directly regulate microtubule lattice integrity under mechanical stress generated by motor protein-driven intracellular transport.

DOI: https://doi.org/10.64898/2026.06.29.735199
Proc Natl Acad Sci U S A. 2026 Jul 14. 123(28): e2533168123

Dendritic morphology and synaptic nonlinearities enhance functional complexity in human cortical neurons.

Ido Aizenbud, Daniela Yoeli, David Beniaguev, Christiaan P J de Kock, Michael London, Idan Segev.

  Humans exhibit unique cognitive abilities within the animal kingdom, but the neural mechanisms driving these advanced capabilities remain poorly understood. Human cortical neurons differ from those of other species, such as rodents, in both their morphological and physiological characteristics. Could the distinct properties of human cortical neurons help explain the superior cognitive capabilities of humans? Understanding this relationship requires a measure to quantify how neuronal properties contribute to the functional complexity of single neurons; yet, such a standardized measure is currently missing. Here, we propose the Functional Complexity Index (FCI), a general, deep-learning-based framework for assessing the input-output complexity of neurons. By comparing the FCI of cortical pyramidal neurons across layers in rats and humans, we identified key morpho-electrical factors that underlie neuronal functional complexity. Human cortical pyramidal neurons are significantly more functionally complex than their rat counterparts, primarily due to differences in dendritic membrane area and branching patterns, as well as in the density and nonlinearity of NMDA-mediated synaptic receptors. These findings reveal the structural and biophysical basis for the enhanced functional properties of human cortical neurons, providing a key step toward understanding the underpinnings of our enhanced cognitive capabilities.

Keywords:  cortical pyramidal neurons; dendritic computation; functional complexity; human neurons; single neuron computation

DOI:  https://doi.org/10.1073/pnas.2533168123
Mol Cell. 2026 Jul 07. pii: S1097-2765(26)00417-X. [Epub ahead of print]

Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.

Dazhi Li, Xinbo Wang, Hongyan Hao, Jessica Eden, Bodan Hu, Emma E Walsh, Matthew A H Parson, Stephanie Hamill, Yuting Li, Guochao Chen, John E Burke, Pietro De Camilli, Karin M Reinisch.

  Bridge-like lipid transfer proteins (BLTPs) play fundamental roles in cellular lipid redistribution between organellar membranes. They comprise bridge domains spanning organelles at contact sites that allow lipids to transit through the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables lipid transfer. To address the mechanisms underlying the assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinson's disease protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, in which the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin (CaM), central to calcium signaling, as a constitutive VPS13C interactor. Calcium induces conformational changes in the VPS13C-CaM complex, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as a starting point for understanding its regulation and that of other VPS13 proteins.

Keywords:  lipid transport; lysosomes, PARK23, Parkinson's disease, BLTP; membrane homeostasis

DOI:  https://doi.org/10.1016/j.molcel.2026.06.028
Front Mol Biosci. 2026 ;13 1849627

Investigating the effect of progressive truncations at the ALS-linked protein TDP-43 RRM2 on its aggregation mechanism.

Greta Grassmann, Matteo Amadei, Arianna Lardieri, Linda Celeste Montemiglio, Alessandra Anna Passeri, Maurizio Mattarelli, Lorenzo Di Rienzo, Mattia Miotto, Giancarlo Ruocco, Edoardo Milanetti.

  Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by inclusions of TDP-43 protein. C-terminal fragments (CTFs) of TDP-43, generated by cleavage within its second RNA recognition motif (RRM2), have been found forming aggregates in patients. Aggregation has often been attributed to the C-terminal domain, but increasing evidence indicates that RRM2 fragments contribute to pathological inclusions. We performed extensive molecular dynamics simulations to investigate the changes resulting from the truncation that could lead to aggregation. We analyzed the full RRM2 domain (fRRM2, residues 192-261) and two fragments commonly observed in CTFs (tRRM2A, residues 220-261, and tRRM2B, residues 209-261). We found that truncation results in distinct aggregation-prone states. tRRM2B appears to rely on β -sheet elements associated with amyloid-like aggregation, whereas tRRM2A exhibits higher structural variability and a reduced β -content, suggesting a phase separation-like aggregation mechanism. We further simulated an extended fragment of tRRM2A, tRRM2A-l (residues 220-269). Although its predicted aggregation propensity remains largely unchanged, tRRM2A-l exhibits increased structural flexibility, and a stronger exposure of Nuclear Export Signal residues. Our results indicate that subtle differences in RRM2 fragment length influence potential misfolding pathways. Future studies and therapeutic strategies to prevent TDP-43 aggregation should carefully consider the specific domain adopted.

Keywords:  ALS (Amyotrophic lateral sclerosis); TDP43; aggregation model; molecular dynamics simulation; protein aggragation; protein structure and function

DOI:  https://doi.org/10.3389/fmolb.2026.1849627
Mol Brain. 2026 Jul 10.

CAST controls presynaptic sequestration of Rab6 in neurons.

Yamato Hida, Atsushi Shimada, Yeon-Jeong Kim, Miyuki Kato-Murayama, Mikako Shirouzu, Toshihisa Ohtsuka.

  CAST is a core active zone scaffold protein, yet its role in Rab6-dependent trafficking remains unclear. Here, we identify the coiled-coil domain of CAST (CC10) as a direct Rab6-binding module and show that CAST selectively interacts with the GTP-bound form of Rab6 in both heterologous cells and neurons. Biochemical mapping, isothermal titration calorimetry, and bimolecular fluorescence complementation demonstrate that CC10 is necessary and sufficient for Rab6 recognition. In cultured hippocampal neurons, CAST promotes the presynaptic accumulation of Rab6, whereas CC10-disrupting mutations abolish this effect without detectably altering Rab6 distribution within axonal regions under our imaging conditions. These results define a CAST-dependent mechanism that spatially restricts Rab6 at presynaptic boutons, extending ELKS-based models of Rab6 cargo capture and providing a structural basis for the organization of presynaptic trafficking.

Keywords:  CAST; Membrane trafficking; Presynaptic bouton; Rab GTPase; Rab6; Synaptic scaffold proteins

DOI:  https://doi.org/10.1186/s13041-026-01330-1
bioRxiv. 2026 Jul 04. pii: 2026.06.30.735662. [Epub ahead of print]

iPSC Neurodegenerative Disease Initiative isogenic CAG repeat iPSC line for Huntington's disease.

Lisa Salazar, Mara S Burns, Jennifer T Stocksdale, Keona Q Wang, Gloria Cao, Ricardo Miramontes, Nicolette R McClure, Leanne Ho, Amber Rose Keith, Margaret Sutherland, Mark R Cookson, Michael Ward, William C Skarnes, Leslie M Thompson.

Purpose of Research: The generation of iPSC lines expressing 21, 56 and 79 glutamine repeats within the HTT protein and homozygous KO of HTT in the KOLF2.1J background as an additional disease series within the iPSC Neurodegenerative Disease Initiative (iNDI) collection.
Major Findings: All iPSCs, even those expressing long repeats of 79Q or HTT KO, were capable of differentiating to striatal and cortical neurons, astrocytes and microglia using established protocols. General quality control stains and morphological analyses are described for each differentiation. A selected set of assays were carried out on differentiated cells; expanded repeat expressing astrocytes showed altered expression of astrocyte protein markers and morphological characteristics, and striatal neurons showed altered DARPP-32/CTIP2 colocalization. mRNAseq carried out for striatal neurons showed high similarities in gene expression changes between 79Q and KO lines compared to the unexpanded repeat.
Conclusions: The KOLF2.1J isogenic CAG repeat series serves as a community resource to study HD mechanisms with the potential for direct comparison across other neurodegenerative diseases through the iNDI collection.

DOI: https://doi.org/10.64898/2026.06.30.735662
Bio Protoc. 2026 Jul 05. 16(13): e5725

Whole-Mount Immunostaining of Tyrosine Hydroxylase for Dopaminergic Neuron Analysis in Zebrafish Larvae.

Luís Félix.

  Whole-mount techniques are widely used in medical and biological research to analyze protein expression and tissue organization in intact specimens. Traditional approaches for protein localization include section-based immunohistochemistry and in situ hybridization; however, these methods can be limited by tissue disruption and loss of spatial context. Whole-mount protocols generally involve tissue fixation, permeabilization, and staining with specific probes, but their effectiveness varies depending on the antigen-antibody combination and the specimen type. Consequently, no universal protocol is suitable for all experimental conditions. This protocol presents a detailed whole-mount immunostaining protocol for evaluating tyrosine hydroxylase (TH) expression, a key marker of dopaminergic neurons, in zebrafish (Danio rerio) larvae. The procedure outlines critical steps from sample preparation to staining optimization to ensure reproducible and specific signal detection. This approach enables accurate visualization and analysis of dopaminergic neuron distribution in intact larvae. The protocol offers a reliable and adaptable approach that preserves tissue integrity, enables three-dimensional visualization, and is particularly well-suited for developmental and neurobiological studies using zebrafish larvae. Key features • Optimized whole-mount immunofluorescence protocol for detecting tyrosine hydroxylase in intact zebrafish larvae. • Permeabilization and bleaching steps were included to improve antibody penetration and reduce pigmentation-related signal interference • Three-dimensional brain architecture is preserved, enabling spatial analysis of dopaminergic neuron distribution without tissue sectioning, including region-specific fluorescence quantification using defined regions of interest (ROIs). • Provides a straightforward approach for assessing dopaminergic neuron distribution through fluorescence imaging and quantitative analysis. • Suitable for neurodevelopmental and neurotoxicity studies using zebrafish larvae.

Keywords:  Dopaminergic neurons; Larvae; Tyrosine hydroxylase; Whole-mount; Zebrafish

DOI:  https://doi.org/10.21769/BioProtoc.5725