Kumar Anmol, Gupta Ajay Kumar, Singh Prashant Kumar
School of Pharmaceutical Science (formerly University Institute of Pharmacy), Chhatrapati Shahu Ji Maharaj University (formerly Kanpur University), Kanpur 208024, India.
Institute of Pharmaceutical Sciences, University of Lucknow, India.
AIMS Neurosci. 2024 Sep 6;11(3):312-340. doi: 10.3934/Neuroscience.2024020. eCollection 2024.
Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons, which leads to motor and non-motor symptoms that have a significant impact. The pathophysiology of PD is complex and involves environmental and genetic factors that contribute to alpha-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. The current treatments of PD primarily focus on symptom management and have limitations in addressing disease progression and non-motor symptoms. Epidemiological data indicates a rise in PD cases worldwide, which highlights the need for effective treatments. Pathophysiological insights point out the involvement of various factors in PD progression, such as dopamine dysregulation, genetic mutations, oxidative stress, mitochondrial damage, alpha-synuclein aggregation, and neuroinflammation. Although current treatments, which include dopamine precursors, monoamine oxidase (MAO) inhibitors, and non-dopaminergic drugs, can alleviate motor symptoms, they are not effective in preventing disease progression or managing non-motor symptoms. Additionally, they can lead to adverse effects and become less effective over time. Novel therapeutic approaches, including cell-based therapies, gene therapies, targeted drug delivery therapies, and magnetic field therapies, are promising in improving symptom management and providing personalized treatment. Additionally, emerging therapies that target alpha-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation may have potential disease-modifying effects. To sum up, for dealing with the multiple aspects of PD, there is a great need to come up with new and creative therapeutic approaches that not only relieve symptoms, but also prevent the progression of disease and non-motor symptoms. The progress made in comprehending the underlying mechanisms of PD provides optimism for developing successful treatments that can enhance the outcomes and quality of life.
帕金森病（PD）是一种神经退行性疾病，涉及多巴胺能神经元的丧失，这会导致产生具有重大影响的运动和非运动症状。PD的病理生理学很复杂，涉及环境和遗传因素，这些因素会导致α-突触核蛋白聚集、线粒体功能障碍、氧化应激和神经炎症。目前PD的治疗主要集中在症状管理方面，在解决疾病进展和非运动症状方面存在局限性。流行病学数据表明全球PD病例呈上升趋势，这凸显了有效治疗的必要性。病理生理学见解指出，多种因素参与了PD的进展，如多巴胺调节异常、基因突变、氧化应激、线粒体损伤、α-突触核蛋白聚集和神经炎症。尽管目前的治疗方法，包括多巴胺前体、单胺氧化酶（MAO）抑制剂和非多巴胺能药物，可以缓解运动症状，但它们在预防疾病进展或管理非运动症状方面并不有效。此外，它们可能会导致不良反应，并且随着时间的推移效果会变差。新的治疗方法，包括基于细胞的疗法、基因疗法、靶向药物递送疗法和磁场疗法，在改善症状管理和提供个性化治疗方面很有前景。此外，针对α-突触核蛋白聚集、线粒体功能障碍和神经炎症的新兴疗法可能具有潜在的疾病修饰作用。总之，为了应对PD的多个方面，迫切需要提出新的、有创造性的治疗方法，这些方法不仅能缓解症状，还能预防疾病进展和非运动症状。在理解PD潜在机制方面取得的进展为开发成功的治疗方法带来了乐观情绪，这些治疗方法可以提高治疗效果和生活质量。
