Calcium homeostasis deregulations in neurodegenerative diseases. AD, PD, HD, and ALS affect cytosolic calcium levels by deregulating different homeostatic control mechanisms. NMDAR or AMPAR activities, calcium buffering proteins, and mitochondrial functions were found to be deregulated in the 4 neurodegenerative conditions. α-Synuclein and Aβ peptides, the building blocks of Lewy bodies in PD and of senile plaques in AD, respectively, can form calcium-permeable ion channels at the plasma membrane. Abnormal ER calcium efflux by a mechanism of oversensitization of InsP3R (in HD and FAD) and RyR (in FAD), or of inactivation of the ER pump SERCA (in FAD), was also observed.