Ordovich-Clarkson Randall D, Jabbour Maurice, Pelayo Daniel Arteaga, Lara Daniel, La Croix Sebastian, Mumman Macie, Stukas Shoshanah, Anderson Reagan, Meraz David, Bangura Anthony, Anderson Brooklyn, Bamrud Luke, Blake Caleb
Faculty at the College of Natural Sciences, Grand Canyon University (GCU), Phoenix, AZ, USA.
Coordinator/Adjunct Faculty at GCU, Phoenix, AZ, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111155. doi: 10.1016/j.pnpbp.2024.111155. Epub 2024 Sep 30.
BACKGROUND & AIM: Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.
The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.
The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.
Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.
帕金森病（PD）的治疗方法大体上一直未变，主要侧重于通过激活多巴胺能通路来缓解症状。目前，尚无经证实的预防PD的方法。本系统评价旨在比较两种不同的化合物，二甲双胍（MTF）和裸盖菇素，作为预防PD发生的潜在治疗药物。
作者进行了一项系统评价，重点关注在细胞和动物模型上测试这些化合物的初步研究，以确定它们是否可能具有任何神经保护或神经可塑性作用。
本评价结果发现，MTF可能通过多种机制阻止PD等疾病的进展，包括在线粒体水平降低氧化应激，从而减少α-突触核蛋白相关损伤。另一方面，裸盖菇素可能通过血清素能通路的心理可塑性激活，特别是5-羟色胺受体激活，增加受损神经元的修复，最终增加脑源性神经营养因子（BDNF）的释放并减少α-突触核蛋白的积累。
本研究的意义包括需要进一步研究MTF的非标签使用，以及进一步研究血清素能化合物如裸盖菇素用于治疗和预防神经退行性疾病。
