Mitochondrial permeability transition pore: a promising target for the treatment of Parkinson’s disease

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• 作者：Md Zeeshan Rasheed ; Heena Tabassum ; Suhel Parvez
• 关键词：Mitochondria ; Permeability transition pore ; Parkinson’s disease ; Reactive oxygen species ; Neurodegenerative diseases ; Apoptosis
• 刊名：Protoplasma
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：254
• 期：1
• 页码：33-42
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Cell Biology; Plant Sciences; Zoology;
• 出版者：Springer Vienna
• ISSN：1615-6102
• 卷排序：254

文摘

Among the neurodegenerative diseases (ND), Parkinson’s disease affects 6.3 million people worldwide characterized by the progressive loss of dopaminergic neurons in substantia nigra. The mitochondrial permeability transition pore (mtPTP) is a non-selective voltage-dependent mitochondrial channel whose opening modifies the permeability properties of the mitochondrial inner membrane. It is recognized as a potent pharmacological target for diseases associated with mitochondrial dysfunction and excessive cell death including ND such as Parkinson’s disease (PD). Imbalance in Ca2+ concentration, change in mitochondrial membrane potential, overproduction of reactive oxygen species (ROS), or mutation in mitochondrial genome has been implicated in the pathophysiology of the opening of the mtPTP. Different proteins are released by permeability transition including cytochrome c which is responsible for apoptosis. This review aims to discuss the importance of PTP in the pathophysiology of PD and puts together different positive as well as negative aspects of drugs such as pramipexole, ropinirole, minocyclin, rasagilin, and safinamide which act as a blocker or modifier for mtPTP. Some of them may be detrimental in their neuroprotective nature.