Update on genetics of amyotrophic lateral sclerosis.
Journal
Current opinion in neurology
ISSN: 1473-6551
Titre abrégé: Curr Opin Neurol
Pays: England
ID NLM: 9319162
Informations de publication
Date de publication:
01 10 2022
01 10 2022
Historique:
pubmed:
10
8
2022
medline:
9
9
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
ALS genetics are highly dynamic and of great interest for the ALS research community. Each year, by using ever-growing datasets and cutting-edge methodology, an array of novel ALS-associated genes and downstream pathomechanisms are discovered. The increasing plenty and complexity of insights warrants regular summary by-reviews. Most recent disease gene discoveries constitute the candidate and risk genes SPTLC1 , KANK1 , CAV1 , HTT , and WDR7 , as well as seven novel risk loci. Cell type and functional enrichment analyses enlighten the genetic basis of selective motor neuron vulnerability in ALS demonstrating high expression of ALS-associated genes in cortical motor neurons and highlight the pathogenic significance of cell-autonomous processes. Major pathomechanistic insights have been gained regarding known ALS genes/proteins, specifically C9orf72 , TDP43, ANXA11 , and KIF5A . The first ASO-based gene-specific therapy trials in familial forms of ALS have yielded equivocal results stressing the re-evaluation of pathomechanisms linked to SOD1 and C9orf72 mutations. The genetic and molecular basis of ALS is increasingly examined on single-cell resolution. In the past 2 years, the understanding of the downstream mechanisms of several ALS genes and TDP-43 proteinopathy has been considerably extended. These insights will result in novel gene specific therapy approaches for sporadic ALS and genetic subtypes.
Identifiants
pubmed: 35942673
doi: 10.1097/WCO.0000000000001093
pii: 00019052-202210000-00018
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
C9orf72 Protein
0
Cytoskeletal Proteins
0
KANK1 protein, human
0
KIF5A protein, human
0
WDR7 protein, human
0
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
672-677Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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