THE ROLE OF DOPAMINE DEFICIENCY IN PARKINSON'S DISEASE AND THE POTENTIAL BENEFITS OF THE KETOGENIC DIET

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, resulting in dopamine deficiency and subsequent motor and non-motor impairments. Although the exact etiology of PD remains unclear, growing evidence implicates a combination of genetic susceptibility, environmental factors, mitochondrial dysfunction, oxidative stress, alpha-synuclein pathology, and dopamine-derived neurotoxicity, including the effects of 3,4-dihydroxyphenylacetaldehyde (DOPAL)(1-2).Dopamine plays a crucial role in the regulation of movement, motivation, cognition, and emotional processing. Its depletion disrupts basal ganglia circuitry, leading to the hallmark motor symptoms of Parkinson’s disease, as well as neuropsychiatric manifestations such as depression, apathy, and cognitive decline.(2-4) Despite significant advances in pharmacological therapies over the past decades, current treatments remain largely symptomatic and do not prevent disease progression.Recent research has increasingly focused on the role of dietary interventions as potential adjunctive therapeutic strategies.(5) Among these, the ketogenic diet has gained attention due to its ability to provide ketone bodies as an alternative energy source for the brain. Nutritional ketosis may improve mitochondrial efficiency, reduce oxidative stress and neuroinflammation, and potentially modulate alpha-synuclein aggregation and dopaminergic neuron vulnerability.This review summarizes current knowledge on the mechanisms underlying dopamine depletion in Parkinson’s disease and explores emerging evidence supporting the ketogenic diet as a complementary approach to conventional therapy.(7) While preliminary findings are encouraging, further well-designed clinical trials are required to establish the efficacy, safety, and long-term benefits of ketogenic dietary interventions in Parkinson’s disease.

帕金森病（Parkinson’s disease, PD）是一种进行性神经退行性疾病，以黑质多巴胺能神经元变性为特征，进而导致多巴胺缺乏及后续的运动与非运动功能障碍。尽管帕金森病的确切病因尚未明确，但越来越多的证据表明，其发病与遗传易感性、环境因素、线粒体功能障碍、氧化应激、α-突触核蛋白（alpha-synuclein）病理改变以及多巴胺源性神经毒性（包括3,4-二羟苯乙醛（3,4-dihydroxyphenylacetaldehyde, DOPAL）的作用）密切相关(1-2)。
多巴胺在调节运动、动机、认知及情绪加工过程中发挥关键作用。其缺乏会破坏基底神经节环路，进而引发帕金森病的标志性运动症状，以及抑郁、情感淡漠、认知衰退等神经精神表现(2-4)。尽管过去数十年间药物治疗取得了显著进展，但当前的治疗手段仍以对症治疗为主，无法阻止疾病进展。近年来，越来越多的研究聚焦于饮食干预作为潜在辅助治疗策略的作用(5)。
其中，生酮饮食（ketogenic diet）因其可为大脑提供酮体作为替代能源而受到广泛关注。营养性酮症（nutritional ketosis）可改善线粒体效能、减轻氧化应激与神经炎症，还可能调节α-突触核蛋白聚集并降低多巴胺能神经元的易感性。
本综述总结了当前关于帕金森病多巴胺缺乏潜在机制的研究进展，并探讨了支持生酮饮食作为常规治疗辅助手段的最新证据(7)。尽管初步研究结果令人鼓舞，但仍需开展设计严谨的临床试验，以明确生酮饮食干预在帕金森病治疗中的有效性、安全性及长期获益。