Molecular pathways to neurodegeneration

Nat Med. 2004 Jul;10 Suppl:S2-9. doi: 10.1038/nm1067.

Abstract

The molecular bases underlying the pathogenesis of neurodegenerative diseases are gradually being disclosed. One problem that investigators face is distinguishing primary from secondary events. Rare, inherited mutations causing familial forms of these disorders have provided important insights into the molecular networks implicated in disease pathogenesis. Increasing evidence indicates that accumulation of aberrant or misfolded proteins, protofibril formation, ubiquitin-proteasome system dysfunction, excitotoxic insult, oxidative and nitrosative stress, mitochondrial injury, synaptic failure, altered metal homeostasis and failure of axonal and dendritic transport represent unifying events in many slowly progressive neurodegenerative disorders.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Peptides / metabolism
  • Protein Deglycase DJ-1
  • Protein Denaturation
  • Protein Folding
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Serum Amyloid A Protein / chemistry
  • Serum Amyloid A Protein / genetics
  • Serum Amyloid A Protein / metabolism
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Oncogene Proteins
  • Peptides
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serum Amyloid A Protein
  • Ubiquitin
  • polyglutamine
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase
  • PARK7 protein, human
  • Protein Deglycase DJ-1