Interactions of Mitochondria/Metabolism and Calcium Regulation in Alzheimer's Disease: A Calcinist Point of View.
Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry. Similar anomalies in calcium result when AD-like changes in mitochondrial enzymes or oxidative stress are induced experimentally. The calcium abnormalities can be directly linked to the altered tau phosphorylation, amyloid precursor protein processing and synaptic dysfunction that are defining features of AD. A better understanding of these changes is required before using calcium abnormalities as therapeutic targets.
Brain and Mind Research Institute, Weill Cornell Medicine, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA. ggibson@med.cornell.edu.
Gary E
http://orcid.org/0000-0003-2549-2876
GE
Gibson
Brain and Mind Research Institute, Weill Cornell Medicine, Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY, 10605, USA.
Ankita
A
Thakkar
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology
D015220:Calcium Channels; D002118:Calcium
Alzheimer’s disease; Amyloid; Calcium; Endoplasmic reticulum; Mitochondria; Presenilin