Converging pathways in neurodegeneration, from genetics to mechanisms.

Journal Article (Journal Article;Review)

Neurodegenerative diseases cause progressive loss of cognitive and/or motor function and pose major challenges for societies with rapidly aging populations. Human genetics studies have shown that disease-causing rare mutations and risk-associated common alleles overlap in different neurodegenerative disorders. Here we review the intricate genotype-phenotype relationships and common cellular pathways emerging from recent genetic and mechanistic studies. Shared pathological mechanisms include defective protein quality-control and degradation pathways, dysfunctional mitochondrial homeostasis, stress granules, and maladaptive innate immune responses. Research efforts have started to bear fruit, as shown by recent treatment successes and an encouraging therapeutic outlook.

Full Text

Duke Authors

Cited Authors

  • Gan, L; Cookson, MR; Petrucelli, L; La Spada, AR

Published Date

  • October 2018

Published In

Volume / Issue

  • 21 / 10

Start / End Page

  • 1300 - 1309

PubMed ID

  • 30258237

Pubmed Central ID

  • PMC6278826

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

Digital Object Identifier (DOI)

  • 10.1038/s41593-018-0237-7


  • eng

Conference Location

  • United States