Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito 170527, Ecuador.
School of Medicine, Universidad Católica Santiago de Guayaquil, Guayaquil 090615, Ecuador.
Nutrients. 2023 Aug 15;15(16):3585. doi: 10.3390/nu15163585.
Parkinson's disease (PD) is a degenerative condition resulting from the loss of dopaminergic neurons. This neuronal loss leads to motor and non-motor neurological symptoms. Most PD cases are idiopathic, and no cure is available. Recently, it has been proposed that insulin resistance (IR) could be a central factor in PD development. IR has been associated with PD neuropathological features like α-synuclein aggregation, dopaminergic neuronal loss, neuroinflammation, mitochondrial dysfunction, and autophagy. These features are related to impaired neurological metabolism, neuronal death, and the aggravation of PD symptoms. Moreover, pharmacological options that involve insulin signaling improvement and dopaminergic and non-dopaminergic strategies have been under development. These drugs could prevent the metabolic pathways involved in neuronal damage. All these approaches could improve PD outcomes. Also, new biomarker identification may allow for an earlier PD diagnosis in high-risk individuals. This review describes the main pathways implicated in PD development involving IR. Also, it presents several therapeutic options that are directed at insulin signaling improvement and could be used in PD treatment. The understanding of IR molecular mechanisms involved in neurodegenerative development could enhance PD therapeutic options and diagnosis.
帕金森病（PD）是一种退行性疾病，源于多巴胺能神经元的丧失。这种神经元的丧失导致运动和非运动性神经系统症状。大多数 PD 病例是特发性的，目前尚无治愈方法。最近，有人提出胰岛素抵抗（IR）可能是 PD 发展的一个核心因素。IR 与 PD 的神经病理学特征有关，如α-突触核蛋白聚集、多巴胺能神经元丧失、神经炎症、线粒体功能障碍和自噬。这些特征与神经代谢受损、神经元死亡和 PD 症状加重有关。此外，还在开发涉及胰岛素信号改善和多巴胺能及非多巴胺能策略的药物选择。这些药物可以预防涉及神经元损伤的代谢途径。所有这些方法都可以改善 PD 的预后。此外，新的生物标志物的鉴定可能允许在高危人群中进行更早的 PD 诊断。本综述描述了涉及 IR 的 PD 发展的主要途径。还介绍了几种针对胰岛素信号改善的治疗选择，可用于 PD 的治疗。对涉及神经退行性发展的 IR 分子机制的理解可以增强 PD 的治疗选择和诊断。
