4.5 Article

Age-related differences in the dynamics of hippocampal proteasome recovery

期刊

JOURNAL OF NEUROCHEMISTRY
卷 123, 期 4, 页码 635-644

出版社

WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2012.07932.x

关键词

hippocampus; immunoproteasome; neurodegen-eration; POMP; proteasome; ubiquitin

资金

  1. Carlos III Health Institute, Spain [PS09/00848]
  2. Spanish Ministry of Education and Science (MEC), Spain
  3. JA
  4. Juan de la Cierva from MICINN, Spain

向作者/读者索取更多资源

Regulation of proteasome abundance to meet cell needs under stress conditions is critical for maintaining cellular homeostasis. However, the effects of aging on this homeostatic response remain unknown. In this report, we analyzed in young and aged rat hippocampus, the dynamics of proteasome recovery induced by proteasome stress. Proteasome inhibition in young rats leads to an early and coordinate transcriptional and translational up-regulation of both the catalytic subunits of constitutive proteasome and the proteasome maturation protein. By contrast, aged rats up-regulated the inducible catalytic subunits and showed a lower and shorter expression of proteasome maturation protein. This resulted in a faster recovery of proteasome activity in young rats. Importantly, proteasome inhibition highly affected pyramidal cells, leading to the accumulation of ubiquitinated proteins in perinuclear regions of aged, but not young pyramidal neurons. These data strongly suggest that age-dependent differences in proteasome level and composition could contribute to neurodegeneration induced by proteasome dysfunction in normal and pathological aging.

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