bims-metalz 2023-10-22 papers

Issue of 2023–10–22
six papers selected by
Mikaila Chetty, Goa University

Biotechnol Appl Biochem. 2023 Oct 17.

Neuroprotective effect of biogenically synthesized ZnO nanoparticles against oxidative stress and β-amyloid toxicity in transgenic Caenorhabditis elegans.

Renuka Mani, Dhineshkumar Ezhumalai, Ganesan Muthusamy, Elangovan Namasivayam.

Amyloid β (Aβ) plaque accumulation-mediated neuronal toxicity has been suggested to cause synaptic damage and consequent degeneration of brain cells in Alzheimer's disease (AD). With the increasing prerequisite of eco-friendly nanoparticles (NPs), research investigators are utilizing green approaches for the synthesis of zinc oxide (ZnO) NPs for pharmaceutical applications. In this present study, ZnO NPs were synthesized from Acanthus ilicifolius to assess the neuroprotective properties in the AD model of transgenic Caenorhabditis elegans strains CL2006 and CL4176 expressing Aβ aggregation. Our findings revealed that the therapeutic effect of green-synthesized ZnO NPs is associated with antioxidant activity. We also found that ZnO NPs significantly enhance the C. elegan's lifespan, locomotion, pharyngeal pumping, chemotaxis behavior also diminish the ROS deposition and intracellular productionMoreover, thioflavin T staining demonstrated that ZnO NPs substantially attenuated the Aβ deposition in the C. elegans strain as compared to untreated worms. With their antioxidant properties, the greenly synthesized ZnO NPs had a significant neuroprotective efficiency on Aβ-induced toxicity by reducing Aβ aggregation and specifically reducing the progression of paralysis in the C. elegans AD model. Our findings suggested that the biosynthesized ZnO NPs could be thought-provoking candidates for age-associated neurodegenerative disorders accompanied by oxidative stress.

Keywords: Acanthus ilicifolius; Alzheimer disease; Caenorhabditis elegans; ZnO nanoparticles; oxidative stress; strickout 8C; β-amyloid

DOI: https://doi.org/10.1002/bab.2527

Neural Regen Res. 2024 Apr;19(4): 833-845

Correlation between the gut microbiome and neurodegenerative diseases: a review of metagenomics evidence.

Xiaoyan Liu, Yi Liu, Junlin Liu, Hantao Zhang, Chaofan Shan, Yinglu Guo, Xun Gong, Mengmeng Cui, Xiubin Li, Min Tang.

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis. As a contributing factor, microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota's diverse microorganisms, and for both neuroimmune and neuroendocrine systems. Here, we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases, with an emphasis on multi-omics studies and the gut virome. The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated. Finally, we discuss the role of diet, prebiotics, probiotics, postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Keywords: biomarker; diet pattern; gut microbiota; gut-brain axis; metagenomics; mitochondrial dysfunction; multi-omics; neurodegenerative disease; neuroinflammation; probiotic

DOI: https://doi.org/10.4103/1673-5374.382223

Cell Death Discov. 2023 Oct 14. 9(1): 376

Abl depletion via autophagy mediates the beneficial effects of quercetin against Alzheimer pathology across species.

Alfonso Schiavi, Claudia Cirotti, Lora-Sophie Gerber, Giulia Di Lauro, Silvia Maglioni, Priscila Yumi Tanaka Shibao, Sabrina Montresor, Janine Kirstein, Patrick Petzsch, Karl Köhrer, Roel P F Schins, Tina Wahle, Daniela Barilà, Natascia Ventura.

Alzheimer's disease is the most common age-associated neurodegenerative disorder and the most frequent form of dementia in our society. Aging is a complex biological process concurrently shaped by genetic, dietary and environmental factors and natural compounds are emerging for their beneficial effects against age-related disorders. Besides their antioxidant activity often described in simple model organisms, the molecular mechanisms underlying the beneficial effects of different dietary compounds remain however largely unknown. In the present study, we exploit the nematode Caenorhabditis elegans as a widely established model for aging studies, to test the effects of different natural compounds in vivo and focused on mechanistic aspects of one of them, quercetin, using complementary systems and assays. We show that quercetin has evolutionarily conserved beneficial effects against Alzheimer's disease (AD) pathology: it prevents Amyloid beta (Aβ)-induced detrimental effects in different C. elegans AD models and it reduces Aβ-secretion in mammalian cells. Mechanistically, we found that the beneficial effects of quercetin are mediated by autophagy-dependent reduced expression of Abl tyrosine kinase. In turn, autophagy is required upon Abl suppression to mediate quercetin's protective effects against Aβ toxicity. Our data support the power of C. elegans as an in vivo model to investigate therapeutic options for AD.

DOI: https://doi.org/10.1038/s41420-023-01592-x

Mol Neurobiol. 2023 Oct 18.

Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases.

Ieshita Pan, Praveen Kumar Issac, Md Mostafizur Rahman, Ajay Guru, Jesu Arockiaraj.

Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.

Keywords: Faecal microbial transplantation; Gut dysbiosis; Neurodegenerative disease; Probiotics

DOI: https://doi.org/10.1007/s12035-023-03691-3

G3 (Bethesda). 2023 Oct 19. pii: jkad241. [Epub ahead of print]

Identification of pararosaniline as a modifier of RNA splicing in Caenorhabditis elegans.

Dylan Huynh, Cheng-Wei Wu.

Post-transcriptional splicing of pre-messenger RNA is an evolutionarily conserved eukaryotic process for producing mature mRNA that is translated into proteins. Accurate splicing is necessary for normal growth and development, and aberrant splicing is increasingly evident in various human pathologies. To study environmental factors that influence RNA splicing, we employed a fluorescent C. elegans in vivo splicing reporter as a biomarker for splicing fidelity to screen against the U.S. EPA ToxCast chemical library. We identified pararosaniline hydrochloride as a strong modifier of RNA splicing. Through gene expression analysis, we found that pararosaniline activates the oxidative stress response and alters the expression of key RNA splicing regulator genes. Physiological assays show that pararosaniline is deleterious to C. elegans development, reproduction, and aging. Through a targeted RNAi screen, we found that inhibiting protein translation can reverse pararosaniline's effect on the splicing reporter and provide significant protection against long-term pararosaniline toxicity. Together, this study reveals a new chemical modifier of RNA splicing and describes translation inhibition as a genetic mechanism to provide resistance.

Keywords: C. elegans ; RNA splicing; Toxcast; aging; pararosaniline; stress

DOI: https://doi.org/10.1093/g3journal/jkad241

iScience. 2023 Oct 20. 26(10): 108067

Distinct pathways for export of silencing RNA in Caenorhabditis elegans systemic RNAi.

Keita Yoshida, Yuji Suehiro, Katsufumi Dejima, Sawako Yoshina, Shohei Mitani.

Dietary supplied double-stranded RNA (dsRNA) can trigger RNA interference (RNAi) systemically in some animals, including the nematode Caenorhabditis elegans. Although this phenomenon has been utilized as a major tool for gene silencing in C. elegans, how cells spread the silencing RNA throughout the organism is largely unknown. Here, we identify two novel systemic RNAi-related factors, REXD-1 and TBC-3, and show that these two factors together with SID-5 act redundantly to promote systemic spreading of dsRNA. Animals that are defective in all REXD-1, TBC-3, and SID-5 functions show strong deficiency in export of dsRNA from intestinal cells, whereas cellular uptake and processing of dsRNA and general secretion events other than dsRNA secretion are still functional in the triple mutant animals. Our findings reveal pathways that specifically regulate the export of dsRNA in parallel, implying the importance of spreading RNA molecules for intercellular communication in organisms.

Keywords: Biochemistry; Biological sciences; Cell biology; Genetics; Molecular biology; Natural sciences

DOI: https://doi.org/10.1016/j.isci.2023.108067