Estradiol rescues male hydroxyl radical-mediated Charcot-Marie-Tooth 2Z by Morc2a stabilization through autophagy inhibition in a murine model.

ABSTRACT: Charcot-Marie-Tooth disease type 2Z (CMT2Z) is an inherited axonal neuropathy caused by haploinsufficiency of microrchidia CW-type zinc finger protein 2 (MORC2), which leads to elevated hydroxyl radical levels, reduced ATPase activity, and apoptosis-mediated neuromuscular degeneration. CMT2Z presents with severe clinical manifestations, yet no widely applicable and affordable treatment has been developed. While gene therapy presents a theoretical solution, its feasibility remains constrained by prohibitive costs and delivery challenges. We observed sex-specific differences in muscle function in a CMT2Z mouse model carrying the microrchidia CW-type zinc finger protein 2A (Morc2a) p.S87L variant, with males exhibiting more severe weakness, suggesting a protective role of estradiol in females

SUBMITTER: Kim JW 

PROVIDER: S-EPMC12321673 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature