Overarching pathomechanisms in inherited peripheral neuropathies, spastic paraplegias, and cerebellar ataxias

Trends Neurosci. 2024 Feb 14:S0166-2236(24)00016-X. doi: 10.1016/j.tins.2024.01.004. Online ahead of print.ABSTRACTInternational consortia collaborating on the genetics of rare diseases have significantly boosted our understanding of inherited neurological disorders. Historical clinical classification boundaries were drawn between disorders with seemingly different etiologies, such as inherited peripheral neuropathies (IPNs), spastic paraplegias, and cerebellar ataxias. These clinically defined borders are being challenged by the identification of mutations in genes displaying wide phenotypic spectra and by shared pathomechanistic themes, which are valuable indications for therapy development. We highlight common cellular alterations that underlie this genetic landscape, including alteration of cytoskeleton, axonal transport, mitochondrial function, and DNA repair response. Finally, we discuss venues for future research using the long axonopathies of the PNS as a model to explore other neurogenetic disorders.PMID:38360512 | DOI:10.1016/j.tins.2024.01.004
Source: Trends in Neurosciences - Category: Neuroscience Authors: Source Type: research