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2000
Volume 14, Issue 1
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by progressive loss of memory and cognitive impairment. Aggregation of amyloid-β (Aβ) peptides is the crucial factor in the onset of AD. The toxic Aβ peptides Aβ40 and Aβ42 are produced from the Aβ precursor protein (APP), a transmembrane protein which is folded and modified in endoplasmic reticulum (ER). ER is the main organelle for the synthesis and processing of nearly all proteins as well as the main cellular source of Ca2+. Under stress conditions, three main ER pathways including inositol- requiring enzyme 1, protein kinase RNA-like ER kinase, and activating transcription factor 6 become activated causing the accumulation of unfolded or misfolded proteins within ER lumen. These pathways manage the stress by regulating the expression of chaperones and enzymes involved in protein folding. Several studies have reported the dysfunction of these stress-sensing pathways in pathological conditions, including neurodegenerative diseases. Recent studies have proposed that neuronal death in AD arises from dysfunction of the ER. Here, we will review recent research findings on the interaction between ER and mitochondria, and its effect on apoptotic pathways. We further provide insights into studies which suggest the role of ER in animal and/or cellular models of AD. Therapeutic strategies that modulate ER could represent a promising approach for prevention or treatment of AD.

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/content/journals/cdt/10.2174/138945013804806532
2013-01-01
2025-05-19
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/content/journals/cdt/10.2174/138945013804806532
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  • Article Type:
    Research Article
Keyword(s): Alzheimer's disease; apoptosis; ATF; ER stress; IRE; PERK; UPR; β-amyloid
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