Vacuolar protein sorting protein 41 (VPS41) at an intersection of endosomal traffic in neurodegenerative disease
Edward F.Griffin
Kim A.Caldwell
Guy A.Caldwell
摘要：Alzheimer's and Parkinson's diseases are neurodegenerative disorders pathologically classified by the accumulation of amyloidogenic proteins into insoluble inclusions within the brain. Specifically, amyloid plaques in the brains of Alzheimer's disease patients are comprised of amyloid-β (Aβ) peptide, the product of sequential cleavage of the amyloid precursor protein by β- and γ-secretases. Similarly, α-synuclein is a major component of Lewy bodies associated with Parkinson's disease. Though both diseases increase progressively with disease and age, the soluble oligomeric forms associated with each polypeptide are, arguably, the most toxic species. Both Aβ and α-synuclein form porous oligomers that permeabilize membranes (Di Scala et al., 2016). Intracellular α-synuclein obstructs endoplasmic reticulum-Golgi traffic and following internalization, Aβ rapidly aggregates in endosomes and lysosomes. Using transgenic Caenorhabditis elegans models of neurodegeneration, Griffin et al. (2018) show that the homotypic fusion protein sorting complex, HOPS, lies at an intersection between the two pathogenic proteins to functionally protect against neurodegeneration (Figure 1).
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论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：3( 1210-1212 )