TY - JOUR
T1 - Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease
AU - Bezprozvanny, Ilya
AU - Mattson, Mark P.
PY - 2008/9
Y1 - 2008/9
N2 - Perturbed neuronal Ca2+ homeostasis is implicated in age-related cognitive impairment and Alzheimer's disease (AD). With advancing age, neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular Ca2+ dynamics. Toxic forms of amyloid β-peptide (Aβ) can induce Ca2+ influx into neurons by inducing membrane-associated oxidative stress or by forming an oligomeric pore in the membrane, thereby rendering neurons vulnerable to excitotoxicity and apoptosis. AD-causing mutations in the β-amyloid precursor protein and presenilins can compromise these normal proteins in the plasma membrane and endoplasmic reticulum, respectively. Emerging knowledge of the actions of Ca2+ upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD.
AB - Perturbed neuronal Ca2+ homeostasis is implicated in age-related cognitive impairment and Alzheimer's disease (AD). With advancing age, neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular Ca2+ dynamics. Toxic forms of amyloid β-peptide (Aβ) can induce Ca2+ influx into neurons by inducing membrane-associated oxidative stress or by forming an oligomeric pore in the membrane, thereby rendering neurons vulnerable to excitotoxicity and apoptosis. AD-causing mutations in the β-amyloid precursor protein and presenilins can compromise these normal proteins in the plasma membrane and endoplasmic reticulum, respectively. Emerging knowledge of the actions of Ca2+ upstream and downstream of Aβ provides opportunities to develop novel preventative and therapeutic interventions for AD.
UR - http://www.scopus.com/inward/record.url?scp=50249135503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=50249135503&partnerID=8YFLogxK
U2 - 10.1016/j.tins.2008.06.005
DO - 10.1016/j.tins.2008.06.005
M3 - Article
C2 - 18675468
AN - SCOPUS:50249135503
SN - 0166-2236
VL - 31
SP - 454
EP - 463
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 9
ER -