Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress

Truncated HSPB1 causes axonal neuropathy and impairs tolerance to unfolded protein stress

BACKGROUND HSPB1 belongs to the family of small heat shock proteins (sHSP) that have importance in protection against unfolded protein stress, in cancer cells for escaping drug toxicity stress and in neurons for suppression of protein aggregates. sHSPs have a conserved α-crystalline domain (ACD), flanked by variable N- and C-termini, whose functions are not fully understood. Dominant missense v...

Truncated small chaperone HSPB1 in peripheral neuropathy: molecular mechanisms and altered cellular pathways

Oxidative Stress Impairs the Heat Stress Response and Delays Unfolded Protein Recovery

BACKGROUND Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability. PRINCIPAL FINDINGS Pretreatment of hydrogen peroxide (H(2)O(2)...

HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation and Interference with the Unfolded Protein Response

BACKGROUND The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hep...

Increased Monomerization of Mutant HSPB1 Leads to Protein Hyperactivity in Charcot-Marie-Tooth Neuropathy*

Small heat shock proteins are molecular chaperones capable of maintaining denatured proteins in a folding-competent state. We have previously shown that missense mutations in the small heat shock protein HSPB1 (HSP27) cause distal hereditary motor neuropathy and axonal Charcot-Marie-Tooth disease. Here we investigated the biochemical consequences of HSPB1 mutations that are known to cause perip...