Open AccessProtein transmission in neurodegenerative disease
Author(s) -
Chao Peng,
John Q. Trojanowski,
Virginia M.Y. Lee
Publication year - 2020
Publication title -
nature reviews. neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.271
H-Index - 150
eISSN - 1759-4766
pISSN - 1759-4758
DOI - 10.1038/s41582-020-0333-7
Subject(s) - amyotrophic lateral sclerosis , disease , pathological , intracellular , amyloid (mycology) , extracellular , medicine , protein aggregation , neuroscience , protein folding , microbiology and biotechnology , biology , pathology
Most neurodegenerative diseases are characterized by the intracellular or extracellular aggregation of misfolded proteins such as amyloid-β and tau in Alzheimer disease, α-synuclein in Parkinson disease, and TAR DNA-binding protein 43 in amyotrophic lateral sclerosis. Accumulating evidence from both human studies and disease models indicates that intercellular transmission and the subsequent templated amplification of these misfolded proteins are involved in the onset and progression of various neurodegenerative diseases. The misfolded proteins that are transferred between cells are referred to as 'pathological seeds'. Recent studies have made exciting progress in identifying the characteristics of different pathological seeds, particularly those isolated from diseased brains. Advances have also been made in our understanding of the molecular mechanisms that regulate the transmission process, and the influence of the host cell on the conformation and properties of pathological seeds. The aim of this Review is to summarize our current knowledge of the cell-to-cell transmission of pathological proteins and to identify key questions for future investigation.