# Genetic commonalities between rare subtypes of ALS and CMT: insights into molecular mechanisms of neurodegeneration

## TL;DR

This paper explores shared genetic factors between two rare neurodegenerative diseases, ALS and CMT, to uncover common molecular mechanisms that could aid in diagnosis and future research.

## Contribution

The study identifies thirteen shared genes and their associated pathways between familial ALS and CMT, revealing potential molecular commonalities.

## Key findings

- Thirteen genes were found to be shared between familial ALS and CMT, involved in processes like axonal transport and protein homeostasis.
- These shared genes suggest common molecular pathways that could explain overlapping features of the two diseases.
- The findings may guide future research into shared mechanisms and improve diagnostic approaches for neurodegenerative disorders.

## Abstract

Amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT) are two distinct neurodegenerative disorders. While ALS is characterised by rapidly progressive motor neuron degeneration, leading to severe complications and death, CMT as a peripheral neuropathy is less severe, and patients have a longer life span, although with a compromised quality of life. Despite their clinical differences, current knowledge suggests that familial ALS (fALS) and CMT may share common genetic and molecular mechanisms. We aimed to identify shared genes mutations and molecular pathways between fALS and CMT through a literature and database search. Thirteen genes were identified, involved in distinct cellular processes: axonal transport (DYNC1H1, KIF5A, SPG11, DCTN1), protein homeostasis (NEFH, VCP, SOD1), RNA metabolism (GARS, SETX), cellular stress response (HSPB1, FIG4), and mitochondrial function (MFN2, CHCHD10). While these linkages to the two diseases are rare for each gene, understanding possible mechanistic commonalities at the molecular level can initiate new research directions, help in identifying additional common genes between neurodegenerative disorders, and improve diagnostics.