The DOI matches its Crossref record; 212 of the 212 references it cites were found in a registry or an index.
The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease
Open accessAbstract
The proteins alpha-synuclein (αSyn) and leucine rich repeat kinase 2 (LRRK2) are both key players in the pathogenesis of the neurodegenerative disorder Parkinson's disease (PD), but establishing a functional link between the two proteins has proven elusive. Research studies for these two proteins have traditionally and justifiably focused in neuronal cells, but recent studies indicate that each protein could play a greater pathological role elsewhere. αSyn is expressed at high levels within neurons, but they also secrete the protein into the extracellular milieu, where it can have broad ranging effects in the nervous system and relevance to disease etiology. Similarly, low neuronal LRRK2 expression and activity suggests that LRRK2-related functions could be more relevant in cells with higher expression, such as brain-resident microglia. Microglia are monocytic immune cells that protect neurons from noxious stimuli, including pathological αSyn species, and microglial activation is believed to contribute to neuroinflammation and neuronal death in PD. Interestingly, both αSyn and LRRK2 can be linked to microglial function. Secreted αSyn can directly activate microglia, and can be taken up by microglia for clearance, while LRRK2 has been implicated in the intrinsic regulation of microglial activation and of lysosomal degradation processes. Based on these observations, the present review will focus on how PD-associated mutations in LRRK2 could potentially alter microglial biology with respect to neuronally secreted αSyn, resulting in cell dysfunction and neurodegeneration.
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“Microglia, the resident immune cells in the brain, also play a role in clearance of α-synuclein, a process which is regulated by LRRK2 kinase activity [46, 71].”
From Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain (2023) · cites this paper as [71]
Experimental — accuracy not yet measuredIn the citing paper
“The clearance of α-syn also can be promoted by the leucine-rich repeat kinase 2 (LRRK2) gene.”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Schapansky et al., 2015
In the citing paper
“Pathogenic mutations in LRRK2 influence the ability of microglia to internalize and degrade α-syn, exacerbating α-syn-induced microglial pathology, and neuroinflammation (Schapansky et al., 2015).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Schapansky et al., 2015
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2 retracted
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Microglia in physiology and disease
Wolf, S. A., Boddeke, H. W. G. M., & Kettenmann, H. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034406 · Cited by 1,426
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Metadata
- Authors
- Schapansky, J., Nardozzi, J. D., & LaVoie, M. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 302
- Pages
- 74-88
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC4383729
- OpenAlex
- W1988160418
- Cited by
- 132
- References
- 212
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 15 · 2019: 15 · 2018: 18 · 2017: 19 · 2016: 14 · 2015: 9
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Michael J. Fox Foundation
- National Institutes of Health (NS072604)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, microglia, alpha-synuclein, LRRK2, microglial activation, neuroinflammation, extracellular alpha-synuclein, lysosomal degradation, LRRK2 mutations, neurodegeneration
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Animals, Humans, Parkinson Disease, Protein Serine-Threonine Kinases, Microglia, alpha-Synuclein
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