Differential proteostasis imbalance and the molecular basis of distinct synucleinopathies and tauopathies.

This short review discusses the structural and molecular events at the origin of diverse debilitating neurodegenerative diseases. The pathological consequences owing to the primary, secondary, tertiary and quaternary structural diversity of alpha-synuclein and tau proteins and the aggregates they form are presented. The crosstalk between alpha-synuclein and tau proteins aggregates structural heterogeneity and cellular homeostasis, and more precisely the proteostasis network is next considered. Overall, the proteostasis network appears as the master regulator of distinct synucleinopathies and tauopathies progression depending on its capacity to clear and/or disassemble to completion structurally diverse alpha-synuclein or tau fibrillar aggregates or not. This article is part of the Theo Murphy meeting issue 'ProteostaSys: a systems view of proteostasis'.