The role of the endoplasmic reticulum in the accumulation of β-amyloid peptide in Alzheimer's disease

Research output: Contribution to journalReview article

37 Citations (Scopus)

Abstract

Increased cerebral levels of Aβ42 peptide, either as soluble or aggregated forms, are suggested to play a key role in the pathogenesis of Alzheimer's disease (AD). The identification of genetic defects in presenilins and β-amyloid precursor protein (β-APP) has led to the development of cellular and animal models that have helped in understanding aspects of the pathophysiology of the inherited early onset forms of AD. However, the majority of AD cases are sporadic with no clear or defined genetic basis. While genetic mutations are responsible for the accumulation of Aβ in early onset AD, the causative factors for accumulation of Aβ in the late onset AD forms are not known. This raises the possibility that Aβ accumulation in the absence of genetic mutations might result from abnormalities that indirectly affect Aβ production or its clearance. Currently, there is no consensus as to what are the mechanisms by which Aβ accumulates or as to which mechanisms underlie Aβ-induced neuronal death in AD. In this review, I will first describe the physiological role of endoplasmic reticulum in the cell and review some of the data supporting dysfunction of the endoplasmic reticulum as an early event leading to Aβ accumulation in familial AD. I will also discuss the possible role of oxidative stress and other factors as contributors in Aβ accumulation by reducing the clearance of Aβ from the endoplasmic reticulum. Finally, I will summarize data that show the endoplasmic reticulum stress as a mechanism underlying exogenous Aβ neurotoxicity.

Original languageEnglish (US)
Pages (from-to)119-133
Number of pages15
JournalCurrent Molecular Medicine
Volume6
Issue number1
DOIs
StatePublished - Feb 1 2006

Fingerprint

Amyloid
Endoplasmic Reticulum
Alzheimer Disease
Peptides
Presenilins
Endoplasmic Reticulum Stress
Oxidative stress
Amyloid beta-Protein Precursor
Consensus
Animals
Oxidative Stress
Animal Models
Defects
Mutation

Keywords

  • Alzheimer's disease
  • Calcium
  • Calreticulin
  • ERAD
  • Endoplasmic reticulum
  • Gadd153
  • UPR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

The role of the endoplasmic reticulum in the accumulation of β-amyloid peptide in Alzheimer's disease. / Othman, Ghribi.

In: Current Molecular Medicine, Vol. 6, No. 1, 01.02.2006, p. 119-133.

Research output: Contribution to journalReview article

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