BIN1 reduction ameliorates DNM2 -related Charcot–Marie–Tooth neuropathy

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(10)

Опубликована: Март 5, 2025

Charcot-Marie-Tooth (CMT) disease, the most common inherited neuromuscular disorder, manifests as progressive muscle weakness and peripheral nerve defects. Dominant mutations in DNM2, encoding large GTPase dynamin 2, result CMT without any suggested therapeutic strategy. Different dominant DNM2 also cause centronuclear myopathy (CNM), increasing BIN1 (amphiphysin 2), an endogenous modulator of rescued CNM mice. Here, we found that level exacerbated phenotypes Dnm2K562E/+ mouse carrying DNM2-CMT mutation. Conversely, whole-body reduction Bin1 expression level, through generation mice with heterozygous loss BIN1, restored motor performance ameliorated organization structural defects nerves. The rescue was maintained at least up to 1 y age. inhibited activity driven by increased K562E mutant, a normalization integrin localization muscle. Overall, this study highlights modifier DNM2-CMT, its potential It revealed opposite pathological mechanism inverse concepts for neuropathy versus DNM2-CNM myopathy.

Язык: Английский

Phosphoinositide signalling in cell motility and adhesion

Nature Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

BIN1 and Alzheimer’s disease: the tau connection

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский