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The pathogenesis of Parkinson's disease

Morris, Huw R; Spillantini, Maria Grazia; Sue, Carolyn M; Williams-Gray, Caroline H; (2024) The pathogenesis of Parkinson's disease. The Lancet , 403 (10423) pp. 293-304. 10.1016/S0140-6736(23)01478-2.

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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.

Type: Article
Title: The pathogenesis of Parkinson's disease
Location: England
DOI: 10.1016/S0140-6736(23)01478-2
Publisher version: http://dx.doi.org/10.1016/s0140-6736(23)01478-2
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10189143
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