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Protein quality control in Alzheimer's disease: a fatal saviour.

Authors
  • Scheper, W1
  • Hol, E M
  • 1 Neurogenetics Laboratory, Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. [email protected] , (Netherlands)
Type
Published Article
Journal
Current drug targets. CNS and neurological disorders
Publication Date
Jun 01, 2005
Volume
4
Issue
3
Pages
283–292
Identifiers
PMID: 15975030
Source
Medline
Language
English
License
Unknown

Abstract

Aggregation of Abeta plays a key role in the pathogenesis of Alzheimer's disease. Although the highly structured Abeta aggregates (fibrils) have long been thought to be the toxic form of Abeta, recent evidence suggests that smaller, soluble intermediates in Abeta aggregation are the real culprit. Because these oligomeric aggregates are already formed in the secretory pathway, this raises another issue: Is intra- or extracellular Abeta involved in the pathogenic cascade? Because aggregated proteins are very toxic, cells have developed quality control responses to deal with such proteins. A prime site for quality culum. Here, aberrant proteins are recognized and can be targeted for degradation to the cytosolic quality control system. In addition, there is accumulating evidence for quality control in other subcellular compartments in the cell. All quality control mechanisms are initially protective, but will become destructive after prolonged accumulation of aggregated proteins. This is enhanced by decreased efficiency of these systems during aging and therefore, these responses may play an important role in the pathogenesis of Alzheimer's disease. In this review, we will discuss the role of protein quality control in the neurotoxicity of Abeta.

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