Induction of neuronal death by ER stress in Alzheimer’s disease

Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

“…ER stress has recently been believed to be involved in the pathogenesis of neurodegenerative diseases including AD (DeGracia and Montie, 2004;Katayama et al, 2004;Lindholm et al, 2006;Smith et al, 2005). e-IF2a is known to be phosphorylated by some kinases including PKR, PERK, HRI, and GCN2 under various stresses such as ER stress (Taylor et al, 2005).…”

“…Prolonged ER stress is linked to the pathogenesis of several neurodegenerative disorders, which include cerebral ischemia, PD, and AD (DeGracia and Montie, 2004;Katayama et al, 2004;Smith et al, 2005).…”

ER stress and neurodegenerative diseases

“…39,40 Recent studies have shown an involvement of ER stress and disturbed calcium homeostasis in AD. 11,39,41 Analyses of brain tissue from AD patients revealed alterations in calcium metabolism that are associated with the neurodegenerative process. Neurons containing NFT showed an increase in the levels of free and protein bound calcium compared with tangle free neuron.…”

“…1-3 IRE activates downstream signals and the transcription of the ER chaperone, 78 kDa glucose-regulated protein (GRP78), also called BiP. 41 Mutant PS1 suppresses the activation of UPR, indicating that the responsiveness of the ER is reduced in the presence of mutant PS1.…”

Stress du réticulum endoplasmique

“…IRE1 intervient également dans les processus de mort cellulaire au cours de maladies neurodégénératives. Ainsi, dans la maladie d'Alzheimer et plus particulièrement sa forme familiale (FAD), les produits de trois gènes ont été identifiés comme étant responsables de cette pathologie : l'amyloid precursor protein (APP), et les présénilines 1 et 2 (PS1 ; PS2), les mutations de la PS1 étant les plus fréquemment rencontrées chez les patients atteint d'une FAD [41]. De plus, des études in vitro ont mis en évidence que les cellules exprimant une forme mutée de PS1 sont plus sensibles aux stimulus apoptiques induits par le stress du RE.…”