Calpain 1 (my-calpain, CAPN1) is a calcium-dependent cysteine protease, which is activated by small changes in calcium concentration. Disrupted intracellular calcium homeostasis leads to hyperactivation of CAPN1. Hyperactivated calpain 1 enhances the accumulation of beta-amyloid peptide by increasing the expression level of beta-secretase (BACE1) and induces hyperphosphorylation of tau along with the formation of neurofibrillary tangle by mediating p35 cleavage into p25, both of which are the major mechanisms of neurodegeneration in Alzheimer's disease (AD). Hence, inhibition of CAPN1 activity is very important in the treatment and prevention of AD. Conjugated linoleic acid (CLA), an eighteen-carbon unsaturated fatty acid, acts as a CAPN1-specific inhibitor.
CIDeRplus
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