The Spectrum of Small Heat Shock Protein B8 (HSPB8)-Associated Neuromuscular Disorders DOI Open Access
Hebatallah R. Rashed, Samir R. Nath, Margherita Milone

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2905 - 2905

Published: March 23, 2025

The heat shock protein B8 (HSPB8) is one of the small proteins (sHSP or HSPB) and a ubiquitous in various organisms, including humans. It highly expressed skeletal muscle, heart, neurons. plays crucial role identifying misfolding participating chaperone-assisted selective autophagy (CASA) for removal misfolded damaged, potentially cytotoxic proteins. Mutations HSPB8 can cause distal hereditary motor neuropathy (dHMN), Charcot-Marie-Tooth (CMT) disease type 2L, myopathy. manifest from childhood to mid-adulthood. Most missense mutations N-terminal α-crystallin domains lead dHMN CMT2L. Frameshift C-terminal domain (CTD), resulting elongation C-terminal, myopathy with myofibrillar pathology rimmed vacuoles. Myopathy coexist. frameshift CTD result mutant aggregation, which weakens CASA ability direct autophagic degradation. Cellular animal models indicate that drive pathogenesis through toxic gain-of-function mechanism. Currently, no cure available HSPB8-associated neuromuscular disorders, but numerous therapeutic strategies are under investigation spanning molecules RNA interference exogenous delivery.

Language: Английский

The Spectrum of Small Heat Shock Protein B8 (HSPB8)-Associated Neuromuscular Disorders DOI Open Access
Hebatallah R. Rashed, Samir R. Nath, Margherita Milone

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2905 - 2905

Published: March 23, 2025

The heat shock protein B8 (HSPB8) is one of the small proteins (sHSP or HSPB) and a ubiquitous in various organisms, including humans. It highly expressed skeletal muscle, heart, neurons. plays crucial role identifying misfolding participating chaperone-assisted selective autophagy (CASA) for removal misfolded damaged, potentially cytotoxic proteins. Mutations HSPB8 can cause distal hereditary motor neuropathy (dHMN), Charcot-Marie-Tooth (CMT) disease type 2L, myopathy. manifest from childhood to mid-adulthood. Most missense mutations N-terminal α-crystallin domains lead dHMN CMT2L. Frameshift C-terminal domain (CTD), resulting elongation C-terminal, myopathy with myofibrillar pathology rimmed vacuoles. Myopathy coexist. frameshift CTD result mutant aggregation, which weakens CASA ability direct autophagic degradation. Cellular animal models indicate that drive pathogenesis through toxic gain-of-function mechanism. Currently, no cure available HSPB8-associated neuromuscular disorders, but numerous therapeutic strategies are under investigation spanning molecules RNA interference exogenous delivery.

Language: Английский

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