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

Authors:
Harish Kumar
Harish Kumar
Amrita Institute of Medical Sciences
India
Jayant B Udgaonkar
Jayant B Udgaonkar
Tata Institute of Fundamental Research
India

Biochim Biophys Acta Proteins Proteom 2019 Apr 12. Epub 2019 Apr 12.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru 560065, India; Indian Institute of Science Education and Research, Pune 411008, India. Electronic address:

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.

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Source
http://dx.doi.org/10.1016/j.bbapap.2019.04.004DOI Listing
April 2019

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