ArticleHuman molecular genetics2018
Distinct functional roles of Vps41-mediated neuroprotection in Alzheimer's and Parkinson's disease models of neurodegeneration.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.Acta neuropathologica · 2025Article
- Dopaminergic neurodegeneration inmicroPublication biology · 2025Article
- A Brief Review on Caenorhabditis elegans Role in Modelling Neurodegenerative Disease.Central nervous system agents in medicinal chemistry · 2025Review
- Comparison of the Amyloid Plaque Proteome in Down Syndrome, Early-Onset Alzheimer's Disease and Late-Onset Alzheimer's Disease.Research square · 2024Article
- A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer's disease.Genome medicine · 2023Article
- Multiple tethers of organelle contact sites are involved in α-synuclein toxicity in yeast.Molecular biology of the cell · 2023Article
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- Genetic control of RNA editing in neurodegenerative disease.Briefings in bioinformatics · 2023Article
- Integrated regulation of dopaminergic and epigenetic effectors of neuroprotection in Parkinson's disease models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.Molecular neurodegeneration · 2023Article
- A mechanosensory defect in amicroPublication biology · 2023Article
- AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.Traffic (Copenhagen, Denmark) · 2023Article
- The amyloid plaque proteome in early onset Alzheimer's disease and Down syndrome.Acta neuropathologica communications · 2022Article
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- Caenorhabditis elegans for rare disease modeling and drug discovery: strategies and strengths.Disease models & mechanisms · 2021Review
- Neurodegenerative VPS41 variants inhibit HOPS function and mTORC1-dependent TFEB/TFE3 regulation.EMBO molecular medicine · 2021Article
- Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration.International journal of molecular sciences · 2021Review
- miR-590-3 and SP1 Promote Neuronal Apoptosis in Patients with Alzheimer's Disease via AMPK Signaling Pathway.Contrast media & molecular imaging · 2021Article
- Modeling neurodegeneration inDisease models & mechanisms · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Commonalities and, in some cases, pathological overlap between neurodegenerative diseases have led to speculation that targeting of underlying mechanisms might be of potentially shared therapeutic benefit. Alzheimer's disease is characterized by the formation of plaques, composed primarily of the amyloid-β 1-42 (Aβ) peptide in the brain, resulting in neurodegeneration. Previously, we have shown that overexpression of the lysosomal-trafficking protein, human Vps41 (hVps41), is neuroprotective in a transgenic worm model of Parkinson's disease, wherein progressive dopaminergic neurodegeneration is induced by α-synuclein overexpression. Here, we report the results of a systematic comparison of hVps41-mediated neuroprotection between α-synuclein and Aβ in transgenic nematode models of Caenorhabditis elegans. Our results indicate that an ARF-like GTPase gene product, ARL-8, mitigates endocytic Aβ neurodegeneration in a VPS-41-dependent manner, rather than through RAB-7 and AP3 as with α-synuclein. Furthermore, the neuroprotective effect of ARL-8 or hVps41 appears to be dependent on their colocalization and the activity of ARL-8. Additionally, we demonstrate that the LC3 orthologue, LGG-2, plays a critical role in Aβ toxicity with ARL-8. Further analysis of functional effectors of Aβ protein processing via the lysosomal pathway will assist in the elucidation of the underlying mechanism involving VPS-41-mediated neuroprotection. These results reveal functional distinctions in the intracellular management of neurotoxic proteins that serve to better inform the path for development of therapeutic interventions to halt neurodegeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.