Cited by 803Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingDeep Brain Stimulation and Movement Disorders

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Parkinson’s disease: genetics and pathogenesis

Shulman, Joshua M., De Jager, Philip L., Feany, Mel B.·2011·Annual Review of Pathology: Mechanisms of Disease

DOI 10.1146/annurev-pathol-011110-130242

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Abstract

Recent investigation into the mechanisms of Parkinson's disease (PD) has generated remarkable insight while simultaneously challenging traditional conceptual frameworks. Although the disease remains defined clinically by its cardinal motor manifestations and pathologically by midbrain dopaminergic cell loss in association with Lewy bodies, it is now recognized that PD has substantially more widespread impact, causing a host of nonmotor symptoms and associated pathology in multiple regions throughout the nervous system. Further, the discovery and validation of PD-susceptibility genes contradict the historical view that environmental factors predominate, and blur distinctions between familial and sporadic disease. Genetic advances have also promoted the development of improved animal models, highlighted responsible molecular pathways, and revealed mechanistic overlap with other neurodegenerative disorders. In this review, we synthesize emerging lessons on PD pathogenesis from clinical, pathological, and genetic studies toward a unified concept of the disorder that may accelerate the design and testing of the next generation of PD therapies.

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Authors: Shulman, J. M., De Jager, P. L., & Feany, M. B.
Affiliations: Broad Institute (US)
Departments of Neurology, Boston, Massachusetts 02115;
Departments of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115;
ORCID: Shulman, Joshua M.
Venue: Annual Review of Pathology: Mechanisms of Disease
Publisher: Annual Reviews
Published: 2011-02-28
Volume: 6
Issue: 1
Pages: 193-222
ISSN: 1553-4006 (ISSN-L)
1553-4014
DOI: 10.1146/annurev-pathol-011110-130242
OpenAlex: W2129917779
Cited by: 801
References: 176
Citations by year: 2026: 10 · 2025: 21 · 2024: 42 · 2023: 34 · 2022: 64 · 2021: 64 · 2020: 46 · 2019: 59 · 2018: 54 · 2017: 59 · 2016: 74 · 2015: 64 · 2014: 56 · 2013: 65 · 2012: 52
FWCI: 8.22
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Pathology Mechanisms of Disease (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
Keywords: Parkinson's disease, susceptibility genes, pathogenesis, dopaminergic neuron loss, Lewy bodies, non-motor symptoms, animal models, neurodegeneration, molecular pathways
MeSH terms: Animals, Humans, Parkinson Disease, Lewy Bodies, Genetic Predisposition to Disease

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