Fig. 1.
Mechanism of calpain activation in various neurodegenerative diseases. Outline of the specific mechanisms that lead to increased intracellular calcium and calpain activation. Ischemia, traumatic brain injury, and epilepsy all cause an acute increase in glutamate release resulting in increased intracellular calcium. The chronic neurodegenerative diseases AD, ALS, and PRE all result in increased NMDA receptor activation, while calcium dysregulation in HD and PD are thought to be due to mitochondrial dysfunction. MS is unique because pathologic calpain activation is initiated by T-cells and propagated by other immune cells such as macrophages and microglia. Examination of calpain activation in MS provides insight into another avenue for calpain activation in neurodegenerative diseases. Aβ amyloid β, AD Alzheimer's disease, ALS amyotrophic lateral sclerosis, Glu glutamate, HD Huntington's disease, INFγ interferon gamma, mhtt mutant huntingtin, MS multiple sclerosis, NMDAR N-methyl-d-aspartate receptor, ROS reactive oxygen species, PD Parkinson's disease, PKC protein kinase C, PRE prion-related encephalopathy, PrP prion-related peptide, PrPSc prion-related peptide, scrapie form