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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 Ca 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. [ABSTRACT FROM AUTHOR]

Stroke is one of the main causes of mortality and disability in most countries of the world. The only way of managing patients with ischemic stroke is the use of intravenous tissue plasminogen activator and endovascular thrombectomy. However, very few patients receive these treatments as the therapeutic time window is narrow after an ischemic stroke. The paucity of stroke management approaches can only be addressed by identifying new possible therapeutic targets. Mitochondria have been a rare target in the clinical management of stroke. Previous studies have only investigated the bioenergetics and apoptotic roles of this organelle; however, the mitochondrion is now considered as a key organelle that participates in many cellular and molecular functions. This review discusses the mitochondrial mechanisms in cerebral ischemia such as its role in reactive oxygen species (ROS) generation, apoptosis, and electron transport chain dysfunction. Understanding the mechanisms of mitochondria in neural cell death during ischemic stroke might help to design new therapeutic targets for ischemic stroke as well as other neurological diseases. [ABSTRACT FROM AUTHOR]