Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Faculty of Health Sciences, School of Medicine, Department of Neurology, University of Pretoria, Pretoria, South Africa.
Eur J Neurosci. 2021 Jul;54(2):4695-4711. doi: 10.1111/ejn.15324. Epub 2021 Jun 23.
A pathological hallmark of the neurodegenerative disorder, Parkinson's disease (PD), is aggregation of toxic forms of the presynaptic protein, α-synuclein in structures known as Lewy bodies. α-Synuclein pathology is found in both the brain and gastrointestinal tracts of affected individuals, possibly due to the movement of this protein along the vagus nerve that connects the brain to the gut. In this review, we discuss current insights into the spread of α-synuclein pathology along the gut-brain axis, which could be targeted for therapeutic interventions. The prion-like propagation of α-synuclein, and the clinical manifestations of gastrointestinal dysfunction in individuals living with PD, are discussed. There is currently insufficient evidence that surgical alteration of the vagus nerve, or removal of gut-associated lymphoid tissues, such as the appendix and tonsils, are protective against PD. Furthermore, we propose curcumin as a potential candidate to prevent the spread of α-synuclein pathology in the body by curcumin binding to α-synuclein's non-amyloid β-component (NAC) domain. Curcumin is an active component of the food spice turmeric and is known for its antioxidant, anti-inflammatory, and potentially neuroprotective properties. We hypothesize that once α-synuclein is bound to curcumin, both molecules are subsequently excreted from the body. Therefore, dietary supplementation with curcumin over one's lifetime has potential as a novel approach to complement existing PD treatment and/or prevention strategies. Future studies are required to validate this hypothesis, but if successful, this could represent a significant step towards improved nutrient-based therapeutic interventions and preventative strategies for this debilitating and currently incurable disorder.
神经退行性疾病帕金森病（PD）的一个病理学特征是，突触前蛋白α-突触核蛋白在称为路易体的结构中聚集形成毒性形式。受影响个体的大脑和胃肠道中都存在α-突触核蛋白病理学，这可能是由于这种蛋白质沿着连接大脑和肠道的迷走神经移动所致。在这篇综述中，我们讨论了目前对α-突触核蛋白病理学沿着肠-脑轴传播的认识，这可能是治疗干预的目标。讨论了α-突触核蛋白的类朊病毒传播以及 PD 患者胃肠道功能障碍的临床表现。目前没有足够的证据表明迷走神经手术改变或切除与肠道相关的淋巴组织（如阑尾和扁桃体）可以预防 PD。此外，我们提出姜黄素作为一种潜在的候选物，通过姜黄素与α-突触核蛋白的非淀粉样β成分（NAC）结构域结合来预防体内α-突触核蛋白病理学的传播。姜黄素是食品香料姜黄的活性成分，以其抗氧化、抗炎和潜在的神经保护特性而闻名。我们假设，一旦α-突触核蛋白与姜黄素结合，这两种分子随后都会从体内排出。因此，一生中用姜黄素进行饮食补充可能是一种补充现有 PD 治疗和/或预防策略的新方法。需要进一步的研究来验证这一假设，但如果成功，这将代表朝着改善基于营养的治疗干预和预防这种使人衰弱且目前无法治愈的疾病的策略迈出了重要一步。
