Tizabi Yousef, Getachew Bruk, Mendieta Liliana, Palafox-Sánchez Victoria, Tsytsarev Vassiliy, Manaye Kebreten F, Tinkov Alexey A, da Silva Victor Diogenes Amaral, Aschner Michael
Department of Pharmacology, Howard University College of Medicine, 520 W Street NW, Washington, DC, 20059, USA.
Laboratorio de Neuroquímica, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, México.
Neurotox Res. 2025 Oct 31;43(6):45. doi: 10.1007/s12640-025-00768-w.
With the advent of medical technology and the sustenance of a longer lifespan, an increase in the number of age-related neurodegenerative diseases, including Parkinson's disease (PD), is inevitable. Although current treatments for PD provide remarkable symptomatic relief for a few years, their side effects, combined with the progression in neurodegeneration, pose an urgent challenge for development of more effective treatments for this devastating disease. The challenge is further exacerbated by the unknown etiology in most PD cases. Nonetheless, progress in early identification of the premorbid/prodromal symptoms as well as understanding processes leading to their manifestation may help provide novel preventive and/or intervention strategies. The triad of the best-characterized and inter-related symptoms of prodromal PD include hyposmia (decrease sense of smell), constipation, and major depressive disorder (MDD). Recent revelations indicate a crucial role for the gut microbiota (GM) not only in maintaining the integrity of the gastrointestinal system but also that of the central nervous system via its bidirectional relationship with the brain, commonly referred to as the gut-brain-axis (GBA). Moreover, neuroinflammation, underscored by microglial activation, is believed to play a critical role in neurodegenerative as well as neuropsychiatric disorders including MDD. Here, we delve into the primary roles of GM/GBA and microglia, as well as their interactions, with the aim of providing novel diagnostic and/or treatments in PD. Regarding the treatments, we mention potential use of pre- post- or pro-biotics, and nicotinic or toll-like receptor modulators.
随着医学技术的进步以及人们寿命的延长，包括帕金森病（PD）在内的与年龄相关的神经退行性疾病数量增加是不可避免的。尽管目前针对PD的治疗在几年内可显著缓解症状，但其副作用，再加上神经退行性变的进展，对开发针对这种毁灭性疾病的更有效治疗方法构成了紧迫挑战。大多数PD病例病因不明，这进一步加剧了这一挑战。尽管如此，在早期识别病前/前驱症状以及了解其表现过程方面取得的进展可能有助于提供新的预防和/或干预策略。前驱PD最具特征且相互关联的三联征症状包括嗅觉减退（嗅觉下降）、便秘和重度抑郁症（MDD）。最近的研究表明，肠道微生物群（GM）不仅在维持胃肠系统的完整性方面，而且通过其与大脑的双向关系（通常称为肠-脑轴，GBA）在维持中枢神经系统的完整性方面都起着关键作用。此外，以小胶质细胞活化为特征的神经炎症被认为在包括MDD在内的神经退行性疾病以及神经精神疾病中起关键作用。在此，我们深入探讨GM/GBA和小胶质细胞的主要作用及其相互作用，旨在为PD提供新的诊断和/或治疗方法。关于治疗方法，我们提到了益生元、益生菌或合生元以及烟碱样或Toll样受体调节剂的潜在用途。
