Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382481, India.
Zydus Research Centre, Cadila Health Care Limited, Sarkhej-Bavla, N.H. 8-A, Moraiya, Ahmedabad, Gujarat 382481, India.
ACS Chem Neurosci. 2023 Jun 7;14(11):1935-1949. doi: 10.1021/acschemneuro.3c00084. Epub 2023 May 25.
Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are α-synuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.
帕金森病（PD）是导致神经退行性变的第二大常见进行性疾病，通常发生在 65 岁以上的人群中。PD 的运动临床症状出现在更晚的阶段，包括僵硬、震颤、运动不能和步态功能障碍。还有非运动症状，如胃肠道和嗅觉功能障碍。然而，由于它们不具有特异性，因此不能将其用于疾病的诊断。PD 的发病机制主要表现为脑黑质致密部（SNpc）多巴胺能（DA）神经元中包含体的沉积。这些包含体的主要成分是α-突触核蛋白聚集体。α-突触核蛋白错误折叠并寡聚化形成聚集体和原纤维。这些聚集体逐渐传播 PD 病理学。这种病理发展的其他显著特征包括线粒体功能障碍、神经炎症、氧化应激和自噬受损。所有这些都导致神经元变性。除此之外，还有许多潜在因素影响这些过程。这些因素包括分子蛋白和信号级联。在这篇综述中，我们列出了一些研究不足的分子靶点，这些靶点可能有助于开发新的和先进的治疗方法。
