PMID- 16472119
OWN - NLM
STAT- MEDLINE
DCOM- 20060525
LR  - 20190922
IS  - 1566-5240 (Print)
IS  - 1566-5240 (Linking)
VI  - 6
IP  - 1
DP  - 2006 Feb
TI  - The role of the endoplasmic reticulum in the accumulation of beta-amyloid peptide 
      in Alzheimer's disease.
PG  - 119-33
AB  - Increased cerebral levels of Abeta(42) 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 
      beta-amyloid precursor protein (beta-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 Abeta in early onset AD, the 
      causative factors for accumulation of Abeta in the late onset AD forms are not 
      known. This raises the possibility that Abeta accumulation in the absence of 
      genetic mutations might result from abnormalities that indirectly affect Abeta 
      production or its clearance. Currently, there is no consensus as to what are the 
      mechanisms by which Abeta accumulates or as to which mechanisms underlie 
      Abeta-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 Abeta accumulation in familial AD. I will also discuss the possible 
      role of oxidative stress and other factors as contributors in Abeta accumulation 
      by reducing the clearance of Abeta from the endoplasmic reticulum. Finally, I 
      will summarize data that show the endoplasmic reticulum stress as a mechanism 
      underlying exogenous Abeta neurotoxicity.
FAU - Ghribi, Othman
AU  - Ghribi O
AD  - Department of Pharmacology, Physiology and Therapeutics, University of North 
      Dakota School of Medicine, Grand Forks, 58202, USA. oghribi@medicine.nodak.edu
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Curr Mol Med
JT  - Current molecular medicine
JID - 101093076
RN  - 0 (Amyloid beta-Peptides)
SB  - IM
MH  - Alzheimer Disease/*metabolism/*pathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Endoplasmic Reticulum/*metabolism
MH  - Hippocampus/cytology/pathology
RF  - 195
EDAT- 2006/02/14 09:00
MHDA- 2006/05/26 09:00
CRDT- 2006/02/14 09:00
PHST- 2006/02/14 09:00 [pubmed]
PHST- 2006/05/26 09:00 [medline]
PHST- 2006/02/14 09:00 [entrez]
AID - 10.2174/156652406775574514 [doi]
PST - ppublish
SO  - Curr Mol Med. 2006 Feb;6(1):119-33. doi: 10.2174/156652406775574514.