Amyloid-β precursor protein facilitates the regulator of calcineurin 1-mediated apoptosis by downregulating proteasome subunit α type-5 and proteasome subunit β type-7

Sep 8, 2014Neurobiology of aging

Amyloid-beta precursor protein may help cell death control by lowering specific protein breakdown components

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Abstract

APP overexpression significantly increased RCAN1 levels in cells and transgenic mice.

  • Individuals with Down syndrome develop Alzheimer's disease neuropathology due to trisomy of chromosome 21.
  • Amyloid-β protein, linked to neuritic plaques, is produced from amyloid-β precursor protein (APP).
  • APP overexpression reduced the expression of two proteasome subunits, potentially leading to impaired degradation of RCAN1.
  • Inhibition of RCAN1 expression diminished APP-induced neuronal cell death.
  • The findings suggest that APP regulates neuronal apoptosis through the proteasome pathway, contributing to Alzheimer's disease in Down syndrome.

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