中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (7): 1210-1212.doi: 10.4103/1673-5374.251329

• 观点:退行性病与再生 • 上一篇    下一篇

空泡分选蛋白41在神经退行性疾病的内体交通的交叉点

  

  • 出版日期:2019-07-15 发布日期:2019-07-15

Vacuolar protein sorting protein 41 (VPS41) at an intersection of endosomal traffic in neurodegenerative disease

Edward F. Griffin 1, Kim A. Caldwell 1, 2, 3, 4, Guy A. Caldwell 1, 2, 3, 4   

  1. 1 Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA;
    2 Departments of Neurology and Neurobiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA;
    3 Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA;
    4 Nathan Shock Center of Excellence for Basic Research in the Biology of Aging, University of Alabama at Birmingham, Birmingham, AL, USA
  • Online:2019-07-15 Published:2019-07-15
  • Contact: Guy A. Caldwell, PhD, gcaldwel@ua.edu.

摘要:

orcid: 0000-0002-8283-9090 (Guy A. Caldwell)

Abstract:

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. Simil arly, 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. 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.