What determines the molecular composition of abnormal protein aggregates in neurodegenerative disease?

Richard A. Armstrong, Peter L. Lantos, Nigel J. Cairns

Research output: Contribution to journalArticle

Abstract

Abnormal protein aggregates, in the form of either extracellular plaques or intracellular inclusions, are an important pathological feature of the majority of neurodegenerative disorders. The major molecular constituents of these lesions, viz., beta-amyloid (Abeta), tau, and alpha-synuclein, have played a defining role in the diagnosis and classification of disease and in studies of pathogenesis. The molecular composition of a protein aggregate, however, is often complex and could be the direct or indirect consequence of a pathogenic gene mutation, be the result of cell degeneration, or reflect the acquisition of new substances by diffusion and molecular binding to existing proteins. This review examines the molecular composition of the major protein aggregates found in the neurodegenerative diseases including the Abeta and prion protein (PrP) plaques found in Alzheimer's disease (AD) and prion disease, respectively, and the cellular inclusions found in the tauopathies and synucleinopathies. The data suggest that the molecular constituents of a protein aggregate do not directly cause cell death but are largely the consequence of cell degeneration or are acquired during the disease process. These findings are discussed in relation to diagnosis and to studies of to disease pathogenesis.
Original languageEnglish
Pages (from-to)351-65
Number of pages15
JournalNeuropathology
Volume28
Issue number4
DOIs
Publication statusPublished - Aug 2008

Fingerprint

Neurodegenerative Diseases
Tauopathies
alpha-Synuclein
Prion Diseases
Inclusion Bodies
Amyloid
Cause of Death
Alzheimer Disease
Cell Death
Mutation
Protein Aggregates
Genes
Proteins

Keywords

  • cellular inclusion
  • disease pathogenesis
  • gene mutation
  • molecular composition
  • neurodegenerative disease
  • protein aggregate

Cite this

Armstrong, Richard A. ; Lantos, Peter L. ; Cairns, Nigel J. / What determines the molecular composition of abnormal protein aggregates in neurodegenerative disease?. In: Neuropathology. 2008 ; Vol. 28, No. 4. pp. 351-65.
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What determines the molecular composition of abnormal protein aggregates in neurodegenerative disease? / Armstrong, Richard A.; Lantos, Peter L.; Cairns, Nigel J.

In: Neuropathology, Vol. 28, No. 4, 08.2008, p. 351-65.

Research output: Contribution to journalArticle

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