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Mechanistic approaches to understand the prion-like propagation of aggregates of the human tau protein

Author:
Kumar, Harish, Udgaonkar, Jayant B.
Source:
Biochimica et biophysica acta 2019 v.1867 no.10 pp. 922-932
ISSN:
1570-9639
Subject:
brain, mutation, neurodegenerative diseases, separation, toxicity
Abstract:
The dynamic nature of the tau protein under physiological conditions is likely to be critical for it to perform its diverse functions inside a cell. Under some conditions, this intrinsically disordered protein assembles into pathogenic aggregates that are self-perpetuating, toxic and infectious in nature. The role of liquid-liquid phase separation in the initiation of the aggregation reaction remains to be delineated. Depending on the nature of the aggregate, its structure, and its localization, neurodegenerative disorders with diverse clinical features are manifested. The prion-like mechanism by which these aggregates propagate and spread across the brain is not well understood. Various factors (PTMs, mutations) have been strongly associated with the pathological aggregates of tau. However, little is known about how these factors modulate the pathological properties linked to aggregation. This review describes the current progress towards understanding the mechanism of propagation of tau aggregates.
Agid:
6381011