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Cyclophilin D as a drug target.
Peter C Waldmeier1, Kaspar Zimmermann, Ting Qian
1Nervous System Research, Novartis Pharma Ltd., CH-4002 Basel, Switzerland. peter.waldmeier@pharma.novartis.com
Current Medicinal Chemistry
|July 23, 2003
Summary
Cyclophilin D (CYP D) is crucial for mitochondrial permeability transition (MPT), a key factor in cell death. Targeting CYP D offers therapeutic potential for injuries and neurodegenerative diseases.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- Mitochondrial permeability transition (MPT) is implicated in cell death pathways.
- Cyclophilin D (CYP D) is a key regulator of the MPT pore.
- Inhibiting MPT shows therapeutic potential for ischemia/reperfusion injury, trauma, and neurodegenerative diseases.
Purpose of the Study:
- To investigate the role of cyclophilin D (CYP D) in mitochondrial permeability transition (MPT).
- To explore the therapeutic potential of targeting CYP D for various diseases.
- To assess the feasibility of designing non-immunosuppressant CYP D ligands.
Main Methods:
- Literature review on MPT, CYP D, and cyclosporin A (CsA) mechanisms.
- Analysis of existing cellular and animal models of MPT-related diseases.
- Structural considerations for drug design targeting CYP D.
Main Results:
- CYP D is an integral component of the MPT pore.
- Cyclosporin A (CsA) inhibits MPT via CYP D, but its cytoprotective effects can be complex.
- Evidence for CsA's in vivo efficacy in MPT-related diseases is less compelling than in vitro.
Conclusions:
- CYP D is a significant drug target for conditions involving MPT.
- Developing specific, non-immunosuppressant CYP D inhibitors is a promising therapeutic strategy.
- Designing brain-penetrant CYP D ligands presents a challenge for neurodegenerative disease treatment.