Numerous studies have deciphered the importance of Cyclophilin D (CypD/ peptidyl prolyl
cis-trans isomerase F) in the formation and regulation of mitochondrial permeability transition pore
(MPTP), implicated in the cell death mechanisms in various neurological diseases. Decrease in the
ATP and increase in the calcium levels are the most common aftermath consequences that are
observed in these diseases. Increased calcium level leads to the persistent opening of MPTP and cell
death, which is mediated by CypD. However, the underlying mechanisms that contribute to the
abnormal calcium homeostasis in different diseases remain elusive. In this review, we attempted to
connect the disruption of mitochondrial bioenergetics with abnormal calcium levels and MPTP.
Further, various proteins that interact with the CypD and the subsequent consequences have been described. All the cell
death pathways in various neurological disorders merge at CypD, which acts as a key regulatory protein in cellular
demise. Agents inhibiting CypD may have a therapeutic potential for treating neurological disorders such as Alzheimer’s
disease, Parkinson’s disease and cerebral ischemia. Further, the knowledge regarding the pathophysiological processes
involved in CypD-regulated MPTP and cell death would assist in battling with these diseases.
Keywords: Apoptosis, calcium homeostasis, cyclosporin A, cyclophilin D, mitochondrial permeability transition pore,
necroptosis, neurological disorders.
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