Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs

Nat Med. 2004 Oct;10(10):1055-63. doi: 10.1038/nm1113.


A wide variety of neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates. More recently, the genetic identification of mutations in familial counterparts to the sporadic disorders, leading to the development of in vitro and in vivo model systems, has provided insights into disease pathogenesis. The effect of many of these mutations is the abnormal processing of misfolded proteins that overwhelms the quality-control systems of the cell, resulting in the deposition of protein aggregates in the nucleus, cytosol and/or extracellular space. Further understanding of mechanisms regulating protein processing and aggregation, as well as of the toxic effects of misfolded neurodegenerative disease proteins, will facilitate development of rationally designed therapies to treat and prevent these disorders.

Publication types

  • Historical Article
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / history
  • Alzheimer Disease / therapy
  • Amyloid beta-Peptides / metabolism
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / history
  • Amyotrophic Lateral Sclerosis / therapy
  • Creutzfeldt-Jakob Syndrome / genetics
  • Creutzfeldt-Jakob Syndrome / history
  • Creutzfeldt-Jakob Syndrome / therapy
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Lewy Bodies / genetics*
  • Lewy Bodies / metabolism
  • Models, Biological*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / history*
  • Neurodegenerative Diseases / therapy*
  • Peptides / metabolism
  • Prions / genetics*
  • Prions / metabolism
  • Protein Folding*
  • Superoxide Dismutase / metabolism
  • Synucleins


  • Amyloid beta-Peptides
  • Nerve Tissue Proteins
  • Peptides
  • Prions
  • Synucleins
  • polyglutamine
  • Superoxide Dismutase