The pathogenesis of Parkinson's disease

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 neuro...

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Bibliographic Details
Published in:The Lancet (British edition) Vol. 403; no. 10423; pp. 293 - 304
Main Authors: Morris, Huw R, Spillantini, Maria Grazia, Sue, Carolyn M, Williams-Gray, Caroline H
Format: Journal Article
Language:English
Published: England Elsevier Ltd 20.01.2024
Elsevier Limited
Subjects:
Aggregates
alpha-Synuclein - metabolism
Alzheimer's disease
Animal diseases
Animal models
Animals
Atrophy
Biomarkers
Brain
Brain - pathology
Brain stem
Dementia
Gene loci
Genetics
Genomes
Humans
Inflammation
Models, Animal
Movement disorders
Mutation
Neurodegenerative diseases
Neurons
Neuropathology
Neuroprotection
Parkinson Disease - etiology
Parkinson Disease - therapy
Parkinson's disease
Pathogenesis
Pathology
Proteins
Synuclein
ISSN:0140-6736, 1474-547X, 1474-547X
Online Access:Get full text
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Summary: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.
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ISSN:0140-6736
1474-547X
1474-547X
DOI:10.1016/S0140-6736(23)01478-2