帕金森病的发病机制。

The pathogenesis of Parkinson's disease.

机构信息

Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK; University College London Movement Disorders Centre, University College London, London, UK; Aligning Science Across Parkinson's Collaborative Research Network, Chevy Chase, MD, USA.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Aligning Science Across Parkinson's Collaborative Research Network, Chevy Chase, MD, USA.

出版信息

Lancet. 2024 Jan 20;403(10423):293-304. doi: 10.1016/S0140-6736(23)01478-2.

DOI:10.1016/S0140-6736(23)01478-2

PMID:38245249

Abstract

Parkinson's disease is a progressive neurodegenerative condition associated with the deposition of aggregated α-synuclein. Insights into the pathogenesis of Parkinson's disease have been derived from genetics and molecular pathology. Biochemical studies, investigation of transplanted neurons in patients with Parkinson's disease, and cell and animal model studies suggest that abnormal aggregation of α-synuclein and spreading of pathology between the gut, brainstem, and higher brain regions probably underlie the development and progression of Parkinson's disease. At a cellular level, abnormal mitochondrial, lysosomal, and endosomal function can be identified in both monogenic and sporadic Parkinson's disease, suggesting multiple potential treatment approaches. Recent work has also highlighted maladaptive immune and inflammatory responses, possibly triggered in the gut, that accelerate the pathogenesis of Parkinson's disease. Although there are currently no disease-modifying treatments for Parkinson's disease, we now have a solid basis for the development of rational neuroprotective therapies that we hope will halt the progression of this disabling neurological condition.

摘要

帕金森病是一种进行性神经退行性疾病，与聚集的α-突触核蛋白的沉积有关。对帕金森病发病机制的深入了解源自遗传学和分子病理学。生化研究、对帕金森病患者移植神经元的研究、细胞和动物模型研究表明，α-突触核蛋白的异常聚集以及病理学在肠道、脑干和大脑高级区域之间的传播可能是帕金森病发展和进展的基础。在细胞水平上，无论是在单基因还是散发性帕金森病中，都可以发现异常的线粒体、溶酶体和内体功能，这表明有多种潜在的治疗方法。最近的工作还强调了适应性免疫和炎症反应的失调，可能是在肠道中触发的，从而加速了帕金森病的发病机制。虽然目前尚无治疗帕金森病的疾病修饰疗法，但我们现在有了合理的神经保护疗法的坚实基础，我们希望这些疗法能够阻止这种使人丧失能力的神经疾病的进展。