Characterizing the Molecular and Mitochondrial Changes in Neuronal Pathology of CMT2D

Jinho Kim

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

Charcot–Marie–Tooth disease type 2D (CMT2D) is a rare, inherited peripheral neuropathy characterized by a spectrum of sensory and motor deficits, including tremor, numbness, pain, and muscle weakness. In CMT2D, reduced translation through chronic activation of the Integrated Stress Response (ISR) is thought to be the primary driver of disease. However, the changes at the molecular level in the diseased state are not well understood. In the present study, we report mitochondrial abnormalities in motor neuron cell bodies, including reduced cristae density and reduced mitochondria count. We also explore the expression of candidate proteins responsible for driving pathology in mitochondria and motor axons. Additionally, we assessed the therapeutic efficacy of 2Bact, an ISR inhibitor drug, which significantly improved neuromuscular junction innervation in Gars mutant mice. Collectively, these findings elucidate the molecular and mitochondrial changes in neuronal pathology of CMT2D.

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