bims-mistre Biomed News
on Mito stress
Issue of 2025–03–02
fifteen papers selected by
Ellen Siobhan Mitchell, MitoQ
  1. Mitochondrial Dysfunction in Neurodegenerative Diseases.
  2. Recent development of mitochondrial metabolism and dysfunction in osteoarthritis.
  3. Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.
  4. The Potential Mechanism of D-Amino Acids - Mitochondria Axis in the Progression of Diabetic Kidney Disease.
  5. How neurons cope with oxidative stress.
  6. Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells.
  7. Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient.
  8. Mitochondrial targeted therapies in MAFLD.
  9. Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health.
  10. Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.
  11. How the Topology of the Mitochondrial Inner Membrane Modulates ATP Production.
  12. The Synergistic Impact of Glycolysis, Mitochondrial OxPhos, and PEP Cycling on ATP Production in Beta Cells.
  13. Regulatory Role of Bioactive Compounds from Natural Spices on Mitochondrial Function.
  14. Brain Glycogen-Its Metabolic Role in Neuronal Health and Neurological Disorders-An Extensive Narrative Review.
  15. Natural Bioactive Compounds Solanesol and Chlorogenic Acid Assembled Nanomicelles for Alzheimer's Disease Therapy.
  1. Cells. 2025 Feb 13. pii: 276. [Epub ahead of print]14(4):
    Mitochondrial Dysfunction in Neurodegenerative Diseases.
    Han-Mo Yang.
      Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical and pathological features, exhibit shared pathways leading to neuronal damage, all of which are closely associated with mitochondrial dysfunction. The high metabolic requirements of neurons make even minor mitochondrial deficiencies highly impactful, driving oxidative stress, energy deficits, and aberrant protein processing. Growing evidence from genetic, biochemical, and cellular investigations associates impaired electron transport chain activity and disrupted quality-control mechanisms, such as mitophagy, with the initial phases of disease progression. Furthermore, the overproduction of reactive oxygen species and persistent neuroinflammation can establish feedforward cycles that exacerbate neuronal deterioration. Recent clinical research has increasingly focused on interventions aimed at enhancing mitochondrial resilience-through antioxidants, small molecules that modulate the balance of mitochondrial fusion and fission, or gene-based therapeutic strategies. Concurrently, initiatives to identify dependable mitochondrial biomarkers seek to detect pathological changes prior to the manifestation of overt symptoms. By integrating the current body of knowledge, this review emphasizes the critical role of preserving mitochondrial homeostasis as a viable therapeutic approach. It also addresses the complexities of translating these findings into clinical practice and underscores the potential of innovative strategies designed to delay or potentially halt neurodegenerative processes.
    Keywords:  mitochondrial dynamics; mitochondrial dysfunction; neurodegenerative disease; oxidative stress
    DOI:  https://doi.org/10.3390/cells14040276
  2. Front Pharmacol. 2025 ;16 1538662
    Recent development of mitochondrial metabolism and dysfunction in osteoarthritis.
    Pengchao Guo, Ahmad Alhaskawi, Safwat Adel Abdo Moqbel, Zhijun Pan.
      Osteoarthritis is a degenerative joint disorder characterized by cartilage degradation, synovial inflammation, and altered subchondral bone structure. Recent insights have identified mitochondrial dysfunction as a pivotal factor in OA pathogenesis, contributing to chondrocyte apoptosis, oxidative stress, and extracellular matrix degradation. Disruptions in mitochondrial dynamics, including impaired biogenesis, mitophagy, and metabolic shifts from oxidative phosphorylation to glycolysis, exacerbate cartilage damage by promoting the production of reactive oxygen species and matrix-degrading enzymes such as ADAMTS and MMPs. This review explores the molecular mechanisms underlying mitochondrial dysfunction in OA, emphasizing its role in cartilage homeostasis and inflammation. Furthermore, it highlights emerging therapeutic strategies targeting mitochondrial pathways, including antioxidants, mitophagy enhancers, and metabolic modulators, as potential interventions to mitigate disease progression, which offer promising avenues for advancing personalized and disease-modifying treatments in OA.
    Keywords:  cartilage degradation; inflammation; mitochondrial dysfunction; mitochondrial metabolism; osteoarthritis
    DOI:  https://doi.org/10.3389/fphar.2025.1538662
  3. Biomedicines. 2025 Jan 31. pii: 327. [Epub ahead of print]13(2):
    Mitochondrial Dysfunction in Neurodegenerative Diseases: Mechanisms and Corresponding Therapeutic Strategies.
    Kai Meng, Haocheng Jia, Xiaoqing Hou, Ziming Zhu, Yuguang Lu, Yingying Feng, Jingwen Feng, Yong Xia, Rubin Tan, Fen Cui, Jinxiang Yuan.
      Neurodegenerative disease (ND) refers to the progressive loss and morphological abnormalities of neurons in the central nervous system (CNS) or peripheral nervous system (PNS). Examples of neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Recent studies have shown that mitochondria play a broad role in cell signaling, immune response, and metabolic regulation. For example, mitochondrial dysfunction is closely associated with the onset and progression of a variety of diseases, including ND, cardiovascular diseases, diabetes, and cancer. The dysfunction of energy metabolism, imbalance of mitochondrial dynamics, or abnormal mitophagy can lead to the imbalance of mitochondrial homeostasis, which can induce pathological reactions such as oxidative stress, apoptosis, and inflammation, damage the nervous system, and participate in the occurrence and development of degenerative nervous system diseases such as AD, PD, and ALS. In this paper, the latest research progress of this subject is detailed. The mechanisms of oxidative stress, mitochondrial homeostasis, and mitophagy-mediated ND are reviewed from the perspectives of β-amyloid (Aβ) accumulation, dopamine neuron damage, and superoxide dismutase 1 (SOD1) mutation. Based on the mechanism research, new ideas and methods for the treatment and prevention of ND are proposed.
    Keywords:  mitochondrial dynamics; mitochondrial energy metabolism; mitochondrial homeostasis imbalance; mitophagy; neurodegenerative diseases
    DOI:  https://doi.org/10.3390/biomedicines13020327
  4. Kidney Int Rep. 2025 Feb;10(2): 343-354
    The Potential Mechanism of D-Amino Acids - Mitochondria Axis in the Progression of Diabetic Kidney Disease.
    Hoang Thuy Linh, Yusuke Nakade, Takashi Wada, Yasunori Iwata.
      Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and stands out as the leading cause of end-stage renal disease worldwide. There is increasing evidence that mitochondrial dysfunction, including impaired mitochondrial biogenesis, dynamics, and oxidative stress, contributes to the development and progression of DKD. D-amino acids (D-AAs), which are enantiomers of L-AAs, have recently been detected in various living organisms and are acknowledged to play important roles in numerous physiological processes in the human body. Accumulating evidence demonstrates that D-AA levels in blood or urine could serve as useful biomarkers for reflecting renal function. The physiological roles of D-AAs are implicated in the regulation of cellular proliferation, oxidative stress, generation of reactive oxygen species (ROS), and innate immunity. This article reviews current evidence relating to D-AAs and mitochondrial dysfunction and proposes a potential interaction and contribution of the D-AAs-mitochondria axis in DKD pathophysiology and progression. This insight could provide novel therapeutic approaches for preventing or ameliorating DKD based on this biological axis.
    Keywords:  D-amino acid; ROS production; diabetic kidney disease; gut microbiota; mitochondria; oxidative stress
    DOI:  https://doi.org/10.1016/j.ekir.2024.11.008
  5. Biol Chem. 2025 Feb 25.
    How neurons cope with oxidative stress.
    Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen.
      Neurons are highly dependent on mitochondrial respiration for energy, rendering them vulnerable to oxidative stress. Reactive oxygen species (ROS), by-products of oxidative phosphorylation, can damage lipids, proteins, and DNA, potentially triggering cell death pathways. This review explores the neuronal vulnerability to ROS, highlighting metabolic adaptations and antioxidant systems that mitigate oxidative damage. Balancing metabolic needs and oxidative stress defenses is critical for neurons, as disruptions are implicated in neurodegenerative diseases. Neurons uniquely modulate metabolic pathways, favoring glycolysis over oxidative phosphorylation in cell bodies, to minimize harmful ROS production. Key antioxidants, including superoxide dismutases and glutathione peroxidases, play crucial roles in neuronal protection, as evident from genetic studies linking deficiencies to neurodegeneration. Notably, neurons have the ability to adapt to oxidative conditions in compartment-specific manners and also utilize ROS as a signaling molecule to promote adaptive synaptic plasticity. Future research should aim to elucidate differential ROS signaling and antioxidant responses across neuronal compartments for improved therapeutic strategies.
    Keywords:  antioxidants; ferroptosis; metabolic adaptations; reactive oxygen species (ROS); redox; structural plasticity
    DOI:  https://doi.org/10.1515/hsz-2024-0146
  6. Life (Basel). 2025 Feb 13. pii: 294. [Epub ahead of print]15(2):
    Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells.
    Ming-Chang Chiang, Yu-Ping Yang, Christopher J B Nicol, Tairui Chiang, Chiahui Yen.
      Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration in PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability to transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), a polyphenolic compound with potent antioxidant and anti-inflammatory properties, has been shown to enhance the therapeutic potential of stem cell (SC)-derived Exos. This study investigated the neuroprotective effects of RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+), a neurotoxin commonly used to model Parkinsonian neurotoxicity. Treating SH-SY5Y cells with MPP+ led to significant reductions in cell viability, mitochondrial dysfunction, increased oxidative stress, and the activation of inflammatory pathways. Treatment with RES-hNSCs-Exos rescued SH-SY5Y cells from MPP+-induced toxicity by improving cell viability, enhancing ATP production, increasing mitochondrial biogenesis, and reducing reactive oxygen species (ROS) generation. The findings also demonstrated the increased expression of essential genes involved in mitochondrial biogenesis, such as PGC1α, NRF1, and Tfam, indicating improved mitochondrial function in the presence of RES-hNSCs-Exos. Further analysis revealed that these protective effects were mediated by activating the AMP-activated protein kinase (AMPK) and Nrf2 signaling pathways, which promoted mitochondrial health and reduced oxidative stress. Moreover, RES-hNSCs-Exos treatment suppressed neuroinflammation by downregulating NLRP3 inflammasome activation and reducing the secretion of pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the results suggest that RES-hNSCs-Exos exhibit potent neuroprotective effects against MPP+-induced neurotoxicity by enhancing mitochondrial function, reducing oxidative stress, and inhibiting neuroinflammation. These findings highlight the potential of hNSCs-Exos as a novel therapeutic strategy for neurodegenerative diseases like PD, with RES as a valuable enhancer of Exos efficacy.
    Keywords:  AMPK; MPP+; exosomes; neuroprotection; resveratrol
    DOI:  https://doi.org/10.3390/life15020294
  7. Aging (Albany NY). 2025 Feb 21. 17
    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient.
    Yun Haeng Lee, Eun Young Jeong, Ye Hyang Kim, Ji Ho Park, Jee Hee Yoon, Yoo Jin Lee, So Hun Lee, Yeon Kyung Nam, So Yoon Cha, Jin Seong Park, So Yeon Kim, Youngjoo Byun, Song Seok Shin, Joon Tae Park.
      Reactive oxygen species (ROS) contribute to aging by mainly damaging cellular organelles and DNA. Although strategies to reduce ROS production have been proposed as important components of anti-aging therapy, effective mechanisms to lower ROS levels have not yet been identified. Here, we screened natural compounds frequently used as cosmetic ingredients to find substances that reduce ROS levels. Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts. A novel mechanism by which M. officinalis extract restores mitochondrial function to reduce ROS, a byproduct of inefficient electron transport, was discovered. The reduction of ROS by M. officinalis extracts reversed senescence-associated phenotypes and skin aging. Then, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects. Honokiol functions as an oxygen radical scavenger through redox processes, also significantly reduced ROS levels by restoring mitochondrial function. In summary, our study identified a novel mechanism by which M. officinalis extract reverses aging and skin aging by reducing ROS through restoring mitochondrial function. These new findings will not only expand our understanding of aging and associated diseases, but also provide new approaches to anti-aging treatments.
    Keywords:  ROS; aging rejuvenation; honokiol; magnolia officinalis; mitochondria
    DOI:  https://doi.org/10.18632/aging.206207
  8. Biochem Biophys Res Commun. 2025 Feb 17. pii: S0006-291X(25)00212-8. [Epub ahead of print]753 151498
    Mitochondrial targeted therapies in MAFLD.
    Sien Lai, Dongsheng Tang, Juan Feng.
      Metabolic dysfunction-associated fatty liver disease (MAFLD) is a clinical-pathological syndrome primarily characterized by excessive accumulation of fat in hepatocytes, independent of alcohol consumption and other well-established hepatotoxic agents. Mitochondrial dysfunction is widely acknowledged as a pivotal factor in the pathogenesis of various diseases, including cardiovascular diseases, cancer, neurodegenerative disorders, and metabolic diseases such as obesity and obesity-associated MAFLD. Mitochondria are dynamic cellular organelles capable of modifying their functions and structures to accommodate the metabolic demands of cells. In the context of MAFLD, the excess production of reactive oxygen species induces oxidative stress, leading to mitochondrial dysfunction, which subsequently promotes metabolic disorders, fat accumulation, and the infiltration of inflammatory cells in liver and adipose tissue. This review aims to systematically analyze the role of mitochondria-targeted therapies in MAFLD, evaluate current therapeutic strategies, and explore future directions in this rapidly evolving field. We specifically focus on the molecular mechanisms underlying mitochondrial dysfunction, emerging therapeutic approaches, and their clinical implications. This is of significant importance for the development of new therapeutic approaches for these metabolic disorders.
    Keywords:  MAFLD; Mitochondria; Targeted therapy
    DOI:  https://doi.org/10.1016/j.bbrc.2025.151498
  9. Mol Biol Rep. 2025 Feb 28. 52(1): 270
    Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health.
    Ahmet Alperen Palabiyik, Esra Palabiyik.
       BACKGROUND: Mitochondrial biogenesis is essential for cellular energy balance and metabolic stability. Its dysregulation is linked to various metabolic and neurodegenerative diseases, making it a significant therapeutic target. Pharmacological approaches aimed at enhancing mitochondrial function have gained attention for their potential to restore cellular metabolism.
    OBJECTIVES: This review examines recent advancements in pharmacological strategies targeting mitochondrial biogenesis, focusing on the roles of PGC-1α, AMPK, and SIRT1, alongside novel therapeutic agents and drug delivery systems.
    METHODS: A systematic review of studies published between 2018 and 2023 was conducted using databases such as PubMed, Web of Science, and Elsevier. Keywords related to mitochondrial biogenesis and pharmacological modulation were used to identify relevant literature.
    RESULTS: Various pharmacological agents, including resveratrol, curcumin, and metformin, activate mitochondrial biogenesis through different pathways. SIRT1 activators and AMPK agonists have shown promise in improving mitochondrial function. Advances in mitochondria-targeted drug delivery systems enhance therapeutic efficacy, yet challenges remain in clinical translation due to the complexity of mitochondrial regulation.
    CONCLUSION: Pharmacological modulation of mitochondrial biogenesis holds therapeutic potential for metabolic and neurodegenerative diseases. While preclinical studies are promising, further research is needed to optimize drug efficacy, delivery methods, and personalized treatment strategies.
    Keywords:  AMPK; Mitochondrial biogenesis; Mitochondrial dysfunction; PGC-1α; SIRT1
    DOI:  https://doi.org/10.1007/s11033-025-10368-8
  10. ACS Omega. 2025 Feb 18. 10(6): 5148-5171
    Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.
    Radhakrishna Reddi Sree, Manjunath Kalyan, Nikhilesh Anand, Sangeetha Mani, Vasavi Rakesh Gorantla, Meena Kishore Sakharkar, Byoung-Joon Song, Saravana Babu Chidambaram.
      Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative disease affecting mostly the elderly population. The main pathological features of AD are the extracellular Aβ plaques generated by APP cleavage through the amyloidogenic pathway, the intracellular neurofibrillary tangles (NFT) resulting from the hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, the actual causes of AD are unknown, but several studies suggest hereditary mutations in PSEN1 and -2, APOE4, APP, and the TAU genes are the major perpetrators. In order to understand the etiology and pathogenesis of AD, various hypotheses are proposed. These include the following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, cholinergic deficiency, and gut dysbiosis. Currently approved therapeutic interventions are donepezil, galantamine, and rivastigmine, which are cholinesterase inhibitors (ChEIs), and memantine, which is an N-methyl-d-aspartate (NMDA) antagonist. These treatment strategies focus on only symptomatic management of AD by attenuating symptoms but not regeneration of neurons or clearance of Aβ plaques and hyperphosphorylated Tau. This review focuses on the pathophysiology, novel therapeutic targets, and disease-altering treatments such as α-secretase modulators, active immunotherapy, passive immunotherapy, natural antioxidant products, nanomaterials, antiamyloid therapy, tau aggregation inhibitors, transplantation of fecal microbiota or stem cells, and microtubule stabilizers that are in clinical trials or still under investigation.
    DOI:  https://doi.org/10.1021/acsomega.4c05527
  11. Cells. 2025 Feb 11. pii: 257. [Epub ahead of print]14(4):
    How the Topology of the Mitochondrial Inner Membrane Modulates ATP Production.
    Raquel Adams, Nasrin Afzal, Mohsin Saleet Jafri, Carmen A Mannella.
      Cells in heart muscle need to generate ATP at or near peak capacity to meet their energy demands. Over 90% of this ATP comes from mitochondria, strategically located near myofibrils and densely packed with cristae to concentrate ATP generation per unit volume. However, a consequence of dense inner membrane (IM) packing is that restricted metabolite diffusion inside mitochondria may limit ATP production. Under physiological conditions, the flux of ATP synthase is set by ADP levels in the matrix, which in turn depends on diffusion-dependent concentration of ADP inside cristae. Computer simulations show how ADP diffusion and consequently rates of ATP synthesis are modulated by IM topology, in particular (i) number, size, and positioning of crista junctions that connect cristae to the IM boundary region, and (ii) branching of cristae. Predictions are compared with the actual IM topology of a cardiomyocyte mitochondrion in which cristae vary systematically in length and morphology. The analysis indicates that this IM topology decreases but does not eliminate the "diffusion penalty" on ATP output. It is proposed that IM topology normally attenuates mitochondrial ATP output under conditions of low workload and can be regulated by the cell to better match ATP supply to demand.
    Keywords:  ATP synthesis; cristae; electron tomography; membrane topology; metabolic modeling; metabolite diffusion; mitochondria
    DOI:  https://doi.org/10.3390/cells14040257
  12. Int J Mol Sci. 2025 Feb 10. pii: 1454. [Epub ahead of print]26(4):
    The Synergistic Impact of Glycolysis, Mitochondrial OxPhos, and PEP Cycling on ATP Production in Beta Cells.
    Vladimir Grubelnik, Jan Zmazek, Marko Marhl.
      Pancreatic beta cells regulate insulin secretion in response to glucose by generating ATP, which modulates ATP-sensitive potassium channels (KATP) channel activity and Ca2+ dynamics. We present a model of ATP production in pancreatic beta cells, focusing on ATP dynamics within the bulk cytosol, submembrane region, and microdomains near KATP channels. ATP is generated through glycolysis, mitochondrial oxidative phosphorylation (OxPhos), and glycolytic pyruvate kinase-mediated phosphoenolpyruvate (PEP) production, supported by PEP cycling between mitochondria and the cytosol. The model examines ATP production in relation to Ca2+ oscillations, elucidating their interdependent dynamics. Our findings demonstrate that both mitochondrial OxPhos and PEP-mediated ATP production contribute substantially to cellular ATP levels. Specifically, glycolysis and mitochondrial OxPhos are crucial for the initial (first-phase) increase in bulk and subplasmalemmal ATP, effectively "filling up" the ATP pool in beta cells. In the second phase, coordinated cycling between OxPhos and PEP pathways enables cost-effective fine-tuning of ATP levels, with localized effects in the KATP channel microdomains. This model addresses and clarifies the recent debate regarding the mechanisms by which sufficient ATP concentrations are achieved to close KATP channels in glucose-stimulated beta cells, offering novel insights into the regulation of energy production and KATP channel activity.
    Keywords:  ATP microdomain; NADPH; anaplerosis; beta cell; model
    DOI:  https://doi.org/10.3390/ijms26041454
  13. J Agric Food Chem. 2025 Feb 28.
    Regulatory Role of Bioactive Compounds from Natural Spices on Mitochondrial Function.
    Liguang Han, Chi-Tang Ho, Muwen Lu.
      Natural spices have gained much attention for their aromatic and pungent flavors as well as their multiple beneficial health effects. As complex organelles that play a central role in energy production, stress response control, cell signal transduction, and metabolism regulation, mitochondria could be regulated by many bioactive components in spices. In this review, the role of mitochondria in maintaining cellular and metabolism homeostasis is summarized. The regulatory effects of mitochondrial function by major bioactive compounds from natural spices are evaluated, including capsaicin, 6-gingerol, 6-shogaol, allicin, quercetin, curcumin, tetrahydrocurcumin, and cinnamaldehyde. The underlying molecular mechanisms are also discussed. This work could enhance our understanding toward health-promoting properties of spice compounds as well as provide new insights into the prevention and treatment of disorders associated with mitochondrial dysfunctions by those nutraceuticals.
    Keywords:  biological functions; mechanisms; metabolism; mitochondrial dysfunction; natural spices
    DOI:  https://doi.org/10.1021/acs.jafc.4c12341
  14. Metabolites. 2025 Feb 13. pii: 128. [Epub ahead of print]15(2):
    Brain Glycogen-Its Metabolic Role in Neuronal Health and Neurological Disorders-An Extensive Narrative Review.
    Ana Isabel Beltran-Velasco.
      Background: Brain glycogen is imperative for neuronal health, as it supports energy demands and metabolic processes. This review examines the pathways involved in glycogen storage and utilization in the central nervous system, emphasizing their role in both physiology and pathology. It explores how alterations in glycogen metabolism contribute to neurological disorders, including neurodegenerative diseases, epilepsy, and metabolic conditions while highlighting the bidirectional interaction between neurons and glia in maintaining brain homeostasis. Methods: A comprehensive search of articles published between 2015 and 2025 was conducted using the following databases: ScienceDirect, Scopus, Wiley, Web of Science, Medline, and PubMed. The selection of relevant studies was based on their focus on brain glycogen metabolism and its role in neurological conditions, with studies that did not meet the inclusion criteria being excluded. Results: The metabolic processes of brain glycogen are subject to rigorous regulation by astrocyte-neuron interactions, thereby ensuring metabolic homeostasis and energy availability. The dysregulation of glycogen storage and mobilization has been implicated in the development of synaptic dysfunction, excitotoxicity, and neurodegeneration in a variety of disorders. For instance, aberrant glycogen accumulation in diseases such as Lafora disease has been associated with severe neurodegeneration, while impaired glycogen mobilization has been shown to exacerbate energy deficits in Alzheimer's and epilepsy. Conclusions: Targeting brain glycogen metabolism represents a promising approach for therapeutic intervention in neurological disorders. However, the translation of these strategies to human models remains challenging, particularly with regard to the long-term safety and specificity of glycogen-targeted therapies.
    Keywords:  brain glycogen; enzyme modulation; epilepsy; glucose metabolism; glycogen metabolism; neurodegenerative diseases; neuroglia; neuronal health; therapeutic strategies
    DOI:  https://doi.org/10.3390/metabo15020128
  15. ACS Appl Mater Interfaces. 2025 Feb 25.
    Natural Bioactive Compounds Solanesol and Chlorogenic Acid Assembled Nanomicelles for Alzheimer's Disease Therapy.
    Chenchen Wang, Xiaowan Zhang, Yurong Zhuang, Xiaolei Song, Shihao Sun, Yong Chen, Guihong Qi, Yinan Yang, Peng Li, Wei Wei.
      Solanesol (Sol) and chlorogenic acid (CHA) are naturally active compounds. Sol exhibits a significant free radical absorption ability and strong antioxidant activity. CHA, a typical phenolic acid, exhibits excellent anticancer, anti-inflammation, and antibacterial properties. Herein, bifunctional nanomicelles (CI@SPK) were skillfully designed to take advantage of the unique properties of Sol and CHA to treat Alzheimer's disease (AD). Hydrophobic Sol was modified with poly(ethylene glycol) to self-assemble into stable nanomicelles (SP). CHA could be encapsulated into the hydrophobic core of these nanomicelles, which increased its bioavailability greatly. Short peptide K (CKLVFFAED) was incorporated (CI@SPK) to facilitate their crossing the blood-brain barrier. Then, CI@SPK targeted the AD lesion area, and CHA was released in greater quantities with the help of IR780 under irradiation with an 808 nm laser, resulting in synergistically scavenging reactive oxygen species (ROS) with Sol. Consequently, the nanomicelles CI@SPK demonstrated capabilities in scavenging ROS, inhibiting β-amyloid (Aβ) aggregation, and eventually modulating microglia phenotype from M1 to M2 to promote Aβ phagocytosis and clearance. In vivo studies indicated that nanomicelles CI@SPK improved the learning and cognitive impairments of APP/PS1 mice by reducing Aβ plaque and inflammation, signifying the potential value of CI@SPK in clinical application for AD treatment.
    Keywords:  Alzheimer’s disease; chlorogenic acid; microglia modulation; nanomicelles; solanesol
    DOI:  https://doi.org/10.1021/acsami.4c22621
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