Abstract
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.
CNS & Neurological Disorders - Drug Targets
Title:CypD: The Key to the Death Door
Volume: 14 Issue: 5
Author(s): Shaik M. Fayaz, Yanamala V. Raj and Rajanikant G. Krishnamurthy
Affiliation:
Keywords: Apoptosis, calcium homeostasis, cyclosporin A, cyclophilin D, mitochondrial permeability transition pore, necroptosis, neurological disorders.
Abstract: 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.
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Cite this article as:
Fayaz M. Shaik, Raj V. Yanamala and Krishnamurthy G. Rajanikant, CypD: The Key to the Death Door, CNS & Neurological Disorders - Drug Targets 2015; 14 (5) . https://dx.doi.org/10.2174/1871527314666150429113239
DOI https://dx.doi.org/10.2174/1871527314666150429113239 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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