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糖酵解:帕金森病的下一个重大突破。

Glycolysis: The Next Big Breakthrough in Parkinson's Disease.

机构信息

Dow Medical College, Dow University of Health Sciences, Mission Road, New Labour Colony Nankwara, Karachi, Pakistan.

CMH Lahore Medical College and Institute of Dentistry, Abdur Rehman Road, Cantt, Lahore, Pakistan.

出版信息

Neurotox Res. 2022 Dec;40(6):1707-1717. doi: 10.1007/s12640-022-00579-3. Epub 2022 Sep 24.

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the death of dopaminergic neurons. Its pathogenesis comprises defects in the physiological pathway of mitophagy and mutations in the genes involved in this process's regulatory mechanism. PD manifests itself with multiple motor and non-motor symptoms, and currently, there are multiple pharmacological treatments, and unconventional non-drug treatments available. The mainstay of Parkinson's disease treatment has centered around directly manipulating neural mechanisms to retain high dopamine levels, either by exogenous administration, increasing intrinsic production, or inhibiting the breakdown of dopamine. In this review, we highlight a new potential biochemical modality of treatment, treating PD through glycolysis. We highlight how terazosin (TZ), via PGK1, increases ATP levels and how enhanced glycolysis serves a neuroprotective role in PD, and compensates for damage caused by mitophagy. We also discuss the role of quercetin, a bioactive flavonoid, in preventing the development of PD, and reversing mitochondrial dysfunction but only so in diabetic patients. Thus, further research should be conducted on glycolysis as a protective target in PD that can serve to not just prevent, but also alleviate the non-dopaminergic signs and symptoms of PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其特征是多巴胺能神经元死亡。其发病机制包括自噬生理途径的缺陷和参与这一过程调节机制的基因突变。PD 表现为多种运动和非运动症状,目前有多种药物和非药物治疗方法。帕金森病治疗的主要方法是通过直接操纵神经机制来维持高多巴胺水平,方法包括外源性给药、增加内源性产生或抑制多巴胺的分解。在这篇综述中,我们强调了一种新的潜在生化治疗模式,即通过糖酵解治疗 PD。我们强调了特拉唑嗪(TZ)如何通过 PGK1 增加 ATP 水平,以及增强的糖酵解如何在 PD 中发挥神经保护作用,并补偿自噬引起的损伤。我们还讨论了生物类黄酮槲皮素在预防 PD 发展和逆转线粒体功能障碍方面的作用,但仅在糖尿病患者中如此。因此,应该对糖酵解作为 PD 的保护靶点进行进一步研究,不仅可以预防,还可以缓解 PD 的非多巴胺能症状。

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