Suppression of aggregate and amyloid formation by a novel intrinsically disordered region in metazoan Hsp110 chaperones.

Molecular chaperones maintain proteostasis by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to numerous neurodegenerative disorders including Alzheimer's, Parkinson's, and Huntington's disease. Hsp110 is related to the canonical Hsp70 class of protein-folding molecular chaperones and interacts with Hsp70 as a nucleotide exchange factor (NEF).

Understanding and exploiting interactions between cellular proteostasis pathways and infectious prion proteins for therapeutic benefit.

Several neurodegenerative diseases of humans and animals are caused by the misfolded prion protein (PrP), a self-propagating protein infectious agent that aggregates into oligomeric, fibrillar structures and leads to cell death by incompletely understood mechanisms. Work in multiple biological model systems, from simple baker's yeast to transgenic mouse lines, as well as studies, has illuminated molecular and cellular modifiers of prion disease. In this review, we focus on intersections between PrP and the proteostasis network, including unfolded protein stress response pathways and roles played by the powerful regulators of protein folding known as protein chaperones.

Roles of the nucleotide exchange factor and chaperone Hsp110 in cellular proteostasis and diseases of protein misfolding.

Cellular protein homeostasis (proteostasis) is maintained by a broad network of proteins involved in synthesis, folding, triage, repair and degradation. Chief among these are molecular chaperones and their cofactors that act as powerful protein remodelers. The growing realization that many human pathologies are fundamentally diseases of protein misfolding (proteopathies) has generated interest in understanding how the proteostasis network impacts onset and progression of these diseases.