The Mechanistic Links Between Proteasome Activity, Aging and Agerelated Diseases
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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