Parkinson's Disease: A Progressive Neurodegenerative Disorder and Structure-Activity Relationship of MAO Inhibitor Scaffolds as an Important Therapeutic Regimen.

Salauddin, Syed Amir Azam Zaidi, Mohammed Ubaid, Saniya Shamim, Mohd Javed Naim, Suruchi Khanna, Ozair Alam
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Abstract

Parkinson's disease is considered an advancing neurodegenerative disorder with unknown causes, and its association with some risk factors, including aging, family history, and exposure to chemicals, makes it the second most common occurring neurodegenerative disorder throughout the world with increasing prevalence. Parkinson's disease is associated with slow movement, rigidity, tremors, imbalance, depression, anxiety, cognitive impairment, orthostasis, hyperhidrosis, sleep disorders, pain, and sensory disturbances. In recent decades, there has been a rise in research on the development of effective and potential therapies for the treatment of Parkinson's disease. An important target for neuroprotection is Monoamine Oxidases (MAO), which hydrolyze neurotransmitters like dopamine and produce very reactive free radicals as a by-product. Aging and neurodegenerative illnesses cause overexpression in the brain, which exacerbates neuronal loss. The treatment of Parkinson's disease with MAO inhibitors has shown promising outcomes. Herein, we reported characteristic features of Parkinson's disease, various treatment strategies, and the SAR of potential drugs that can be explored further as lead for the development of newer molecules with improved pharmacological profiles.

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帕金森病:帕金森病:一种进行性神经退行性疾病和作为重要治疗方案的 MAO 抑制剂支架的结构-活性关系。
帕金森病被认为是一种病因不明的渐进性神经退行性疾病,它与一些风险因素(包括衰老、家族史和接触化学物质)有关,因此是全球第二大最常见的神经退行性疾病,而且发病率越来越高。帕金森病与运动迟缓、僵直、震颤、失衡、抑郁、焦虑、认知障碍、正位、多汗、睡眠障碍、疼痛和感觉障碍有关。近几十年来,有关开发治疗帕金森病的有效和潜在疗法的研究不断增加。神经保护的一个重要靶点是单胺氧化酶(MAO),它能水解多巴胺等神经递质,并产生活性很强的自由基作为副产品。衰老和神经退行性疾病会导致单胺氧化酶在大脑中过度表达,从而加剧神经元的损失。用 MAO 抑制剂治疗帕金森病已显示出良好的疗效。在此,我们报告了帕金森病的特征、各种治疗策略以及潜在药物的 SAR,这些药物可作为开发药理特征更佳的新分子的先导药物进行进一步探索。
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