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Curr Genomics. 2014 Feb;15(1):38-51. doi: 10.2174/138920291501140306113344.

The Mechanistic Links Between Proteasome Activity, Aging and Age-related Diseases.

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1
Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Co-logne, Joseph Stelzmann Strasse 26, 50931 Cologne, Germany.

Abstract

Damaged and misfolded proteins accumulate during the aging process, impairing cell function and tissue homeostasis. These perturbations to protein homeostasis (proteostasis) are hallmarks of age-related neurodegenerative disorders such as Alzheimer's, Parkinson's or Huntington's disease. Damaged proteins are degraded by cellular clearance mechanisms such as the proteasome, a key component of the proteostasis network. Proteasome activity declines during aging, and proteasomal dysfunction is associated with late-onset disorders. Modulation of proteasome activity extends lifespan and protects organisms from symptoms associated with proteostasis disorders. Here we review the links between proteasome activity, aging and neurodegeneration. Additionally, strategies to modulate proteasome activity and delay the onset of diseases associated to proteasomal dysfunction are discussed herein.

KEYWORDS:

Aging; Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; Proteasome; Proteostasis; Stem cells.

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