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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Novel Treatments in Subarachnoid Hemorrhage
The current landscape of therapeutic strategies for subarachnoid hemorrhage (SAH), a significant adverse neurological event commonly resulting from the rupture of intracranial aneurysms, is rapidly evolving. Through an in-depth exploration of the natural history of SAH, historical treatment approaches, and emerging management modalities, the present work aims to provide a ...read more
Pathogenic Proteins in Neurodegenerative Diseases: From Mechanisms to Treatment Modalities
The primary objective of this thematic issue is to elucidate the molecular mechanisms by which pathogenic proteins contribute to neurodegenerative diseases and to highlight current and emerging therapeutic strategies aimed at mitigating their effects. By bringing together cutting-edge research and reviews, this issue aims to: 1.Enhance Understanding: Provide a comprehensive ...read more
Role of glial cells in autism spectrum disorder: Molecular mechanism and therapeutic approaches
Emerging evidence suggests that glial cells may play a pivotal role in neuroanatomical and behavioral changes found in autism spectrum disorder (ASD). Many individuals with ASD experience a neuro-immune system abnormalities throughout life, which implicates a potential role of microglia in the pathogenesis of ASD. Dysfunctional astrocytes and oligodendrocytes were ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Targeting the p53 Pathway of Apoptosis
Current Pharmaceutical Design Interactions of VDAC with Proteins Involved in Neurodegenerative Aggregation: An Opportunity for Advancement on Therapeutic Molecules
Current Medicinal Chemistry Group I Metabotropic Glutamate Receptor Signalling and its Implication in Neurological Disease
CNS & Neurological Disorders - Drug Targets Should STEMI Patients Receive Opiate Analgesia? The Morphine Paradox
Current Vascular Pharmacology The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential
Current Medicinal Chemistry Medicinal Chemistry and Anti-Inflammatory Activity of Nitric Oxide-Releasing NSAI Drugs
Mini-Reviews in Medicinal Chemistry Modulation of Inflammation as a Way of Delaying Alzheimer's Disease Progression: The Diet's Role
Current Alzheimer Research Cellular Delivery In Vivo of siRNA-Based Therapeutics
Current Pharmaceutical Design Impact of COX-2 Inhibitors in Common Clinical Practice a Gastroenterologists Perspective
Current Topics in Medicinal Chemistry Subject Index to Volume 9
Current Pharmaceutical Design Pharmacological Modulation of Nitric Oxide Release: New Pharmacological Perspectives, Potential Benefits and Risks
Current Medicinal Chemistry The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer
Current Cancer Drug Targets Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?
Current Neuropharmacology Metabolomics and Heart Diseases: From Basic to Clinical Approach
Current Medicinal Chemistry Electromagnetic Fields Act Similarly in Plants as in Animals: Probable Activation of Calcium Channels via Their Voltage Sensor
Current Chemical Biology Berberine Ameliorates Cognitive Impairment by Regulating Microglial Polarization and Increasing Expression of Anti-inflammatory Factors following Permanent Bilateral Common Carotid Artery Occlusion in Rats
CNS & Neurological Disorders - Drug Targets Sulfur-containing Secondary Metabolites as Neuroprotective Agents
Current Medicinal Chemistry The Protective Effects and Mechanism of Resveratrol-loaded Nanoparticles on HK-2 Cells Suffering from Hypoxia-reoxygenayion
Current Signal Transduction Therapy Experimental Benefits of Sex Hormones on Vascular Function and the Outcome of Hormone Therapy in Cardiovascular Disease
Current Cardiology Reviews Editorial [Hot Topic Management of Perioperative Systemic Inflammation During Cardiopulmonary Bypass: We Need a Multimodal Approach (Guest Editor: David Faraoni)]
Recent Patents on Cardiovascular Drug Discovery