Cited by 86Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroinflammation and Neurodegeneration Mechanisms

Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease

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Kumaran, Ravindran, Cookson, Mark R.·2015·Human Molecular Genetics

Abstract

In the past few years, there have been a large number of genes identified that contribute to the lifetime risk of Parkinson's disease (PD). Some genes follow a Mendelian inheritance pattern, but others are risk factors for apparently sporadic PD. Here, we will focus on those genes nominated by genome-wide association studies (GWAS) in sporadic PD, with a particular emphasis on genes that overlap between familial and sporadic disease such as those encoding a-synuclein (SNCA), tau (MAPT), and leucine-rich repeat kinase 2 (LRRK2). We will advance the view that there are likely relationships between these genes that map not only to neuronal processes, but also to neuroinflammation. We will particularly discuss evidence for a role of PD proteins in microglial activation and regulation of the autophagy-lysosome system that is dependent on microtubule transport in neurons. Thus, there are at least two non-mutually exclusive pathways that include both non-cell-autonomous and cell-autonomous mechanisms in the PD brain. Collectively, these data have highlighted the amount of progress made in understanding PD and suggest ways forward to further dissect this disorder.

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Authors
Kumaran, R., & Cookson, M. R.
Affiliations
National Institutes of Health (US)
Corresponding author
Cookson, Mark R.
Venue
Human Molecular Genetics
Published
2015-06-22
Volume
24
Issue
R1
Pages
R32-R44
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W1757839782
Cited by
86
References
136
Citations by year
2026: 3 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 23 · 2016: 10
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Human Molecular Genetics (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • Intramural Research Program
  • NIH
  • National Institute of Aging
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Parkinson's disease, sporadic Parkinson's disease, familial Parkinson's disease, genetic risk factors, alpha-synuclein, tau protein, MAPT, LRRK2, neuroinflammation, microglial activation, autophagy-lysosome system, microtubule transport, non-cell-autonomous mechanisms, cell-autonomous mechanisms
MeSH terms
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Animals, Humans, Inflammation, Parkinson Disease, tau Proteins, Protein Serine-Threonine Kinases, Autonomic Pathways, Parkinsonian Disorders, alpha-Synuclein, Metabolic Networks and Pathways, Genome-Wide Association Study

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