Evidence map›Paper›PMID 25284317›Full record

ReviewNeuroscience2015

The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease.

J Schapansky, J D Nardozzi, M J LaVoie

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 2 pooled it
9.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Intensive multidisciplinary rehabilitation modulates serumFrontiers in cellular neuroscience · 2026
    Article
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  10. Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
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  12. Article
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  16. Article
  17. Review
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

J SchapanskyCenter for Neurologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA 02115, United States.
J D NardozziCenter for Neurologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA 02115, United States.
M J LaVoieCenter for Neurologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA 02115, United States. Electronic address: mlavoie@rics.bwh.harvard.edu.
Brigham and Women's Hospital · US

Funding

Role of Parkin in Familial and Idiopathic Parkinson's DiseaseR01NS065013 · NINDS · UNIVERSITY OF FLORIDA · PI LAVOIE, MATTHEW J · 2010 to 2020
$3.8M
Regulation of Leucine Rich Repeat Kinase 2 (LRRK2)R21NS072604 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI LAVOIE, MATTHEW J · 2011 to 2012
$491k
NINDS NIH HHS NS072604NINDS NIH HHS R01 NS065013NINDS NIH HHS R21 NS072604
6 · The paper itself

Abstract

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.

Indexed as

alpha-SynucleinAnimalsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MicrogliaParkinson DiseaseProtein Serine-Threonine Kinasesalpha-SynucleinLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Serine-Threonine KinasesautophagyLRRK2microglianeurodegenerationneuroinflammationsynuclein

Identifiers

PMID25284317
PMCPMC4383729
OpenAlexW1988160418

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.