How to Stabilize Both the Proteins and the Membranes: Diverse Effects of sHsps in Neuroprotection

Abstract

Small heat shock proteins (sHsps) are ubiquitously expressed evolutionarily conserved proteins which are upregulated by different stressors and in various pathological conditions in the brain. The most important function of sHsps is to inhibit the aggregation of incorrectly folded proteins by binding to non-native proteins, and to maintain them in a refolding-competent state. They also exhibit anti-apoptotic, antioxidant activities and can bind to the cytoskeleton and membranes, stabilizing and protecting them against stress. These properties enable sHsps to protect neurons against various brain damaging effects. Here, we summarize our current view on the role of sHsps in neurodegeneration, chaperon function, membrane protection, oxidative stress, apoptosis, protein degradation, insulin resistance and blood-brain barrier function. sHsps in NeurodegenerationSmall heat shock proteins (sHsps) are ubiquitously expressed evolutionarily conserved proteins which are upregulated by different stressors and in various patho logical conditions in the brain. The family of sHsps consists of 11 members, characterized by a conserved crystallin domain fl anked by variable N-and C-termini

Heat Shock Proteins and Autophagy Pathways in Neuroprotection: From Molecular Bases to Pharmacological Interventions

“…In addition, Hsps co-localize with the abnormal protein aggregates (reviewed by [ 26 , 137 ]) . In fact, several members of the small Hsp family, such as HspB1, HspB2, HspB5, and HspB6 associate with senile plaques in the AD brain [ 138 ].…”

Dihydropyridines Allosterically Modulate Hsp90 Providing a Novel Mechanism for Heat Shock Protein Co-induction and Neuroprotection

“…The chaperone network helps maintain protein homeostasis (proteostasis) by aiding protein folding, by clearing aggregated and damaged protein from cells and by maintaining proteins in an active state (Hartl, 1996 ; Kim et al, 2013 ; Penke et al, 2018 ). However, with age there is a decline in the capacity of cells to maintain proteostasis and the prevalence of neurodegenerative diseases such as Alzheimer's- (AD) and Parkinson's-disease increases (Valastyan and Lindquist, 2014 ; Toth et al, 2015 ; Hartl, 2017 ). Heat shock proteins have been shown to decrease age-related proteotoxicity, while simultaneously increasing the life span in organisms such as Caenorhabditis elegans (Murshid et al, 2013 ).…”