CoChat
Sign Up
Cited by 252Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingDeep Brain Stimulation and Movement Disorders

The DOI matches its Crossref record; 127 of the 127 references it cites were found in a registry or an index.

The role of the LRRK2 gene in Parkinsonism

Open access
Li, Jie-Qiong, Tan, Lan, Yu, Jin-Tai·2014·Molecular Neurodegeneration
DOI 10.1186/1750-1326-9-47PMC PMC4246469
Open this paper in CoChat — free account

Abstract

Parkinson's disease (PD), like many common age-related conditions, has been recognized to have a substantial genetic component. Multiple lines of evidence suggest that Leucine-rich repeat kinase 2 (LRRK2) is a crucial factor to understanding the etiology of PD. LRRK2 is a large, widely expressed, multi-domain and multifunctional protein. LRRK2 mutations are the major cause to inherited and sporadic PD. In this review, we discuss the pathology and clinical features which show diversity and variability of LRRK2-associated PD. In addition, we do a thorough literature review and provide theoretical data for gene counseling. Further, we present the evidence linking LRRK2 to various possible pathogenic mechanism of PD such as α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction as well as autophagy-lysosomal system. Based on the above work, we investigate activities both within GTPase and outside enzymatic regions in order to obtain a potential therapeutic approach to solve the LRRK2 problem.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1750-1326-9-47

Cites

127 of 127 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Schematic representation of LRRK2 and the pathogenic mutations associated with PD ARM, Armadillo; ANK, Ankyrin repeat; LRR, leucine-rich repeat; ROC, Ras of complex proteins: GTPase; COR, C-terminal of ROC; WD40, WD-40 domain. Potential pathogenic mutations are shown together.
Figure 1 Schematic representation of LRRK2 and the pathogenic mutations associated with PD ARM, Armadillo; ANK, Ankyrin repeat; LRR, leucine-rich repeat; ROC, Ras of complex proteins: GTPase; COR, C-terminal of ROC; WD40, WD-40 domain. Potential pathogenic mutations are shown together.CC BY · PubMed Central
Figure 2 LRRK2-mediated the phosphorylation of tubulin-associated tau LRRK2 interacts with tubulin-associated tau, resulting in the formation of a tripartite complex. The interaction between LRRK2 and β-tubulin is mediated by the LRRK2 Roc domain and β-tubulin C termini. Tubulin-associated tau was phosphorylated by LRRK2. LRRK2 interacted directly with GSK-3β, and that His–GSK-3β bound to the kinase domain of LRRK2 (thick line). Phosphorylation of tau by GSK-3β was stimulated by LRRK2 (thin arrow). P.G2019S-LRRK2 had higher binding affinity for GSK-3β and showed much stronger stimulatory activity (thick line and arrow).
Figure 2 LRRK2-mediated the phosphorylation of tubulin-associated tau LRRK2 interacts with tubulin-associated tau, resulting in the formation of a tripartite complex. The interaction between LRRK2 and β-tubulin is mediated by the LRRK2 Roc domain and β-tubulin C termini. Tubulin-associated tau was phosphorylated by LRRK2. LRRK2 interacted directly with GSK-3β, and that His–GSK-3β bound to the kinase domain of LRRK2 (thick line). Phosphorylation of tau by GSK-3β was stimulated by LRRK2 (thin arrow). P.G2019S-LRRK2 had higher binding affinity for GSK-3β and showed much stronger stimulatory activity (thick line and arrow).CC BY · PubMed Central
Figure 3 The possible pathogenic mechanism links LRRK2 and Parkinson’s disease α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction and autophagy-lysosomal system all take part in the pathogenic of PD. Open and filled arrows show positive (activating) and negative (suppressing) interactions, respectively.
Figure 3 The possible pathogenic mechanism links LRRK2 and Parkinson’s disease α-synuclein, tau, inflammatory response, oxidative stress, mitochondrial dysfunction, synaptic dysfunction and autophagy-lysosomal system all take part in the pathogenic of PD. Open and filled arrows show positive (activating) and negative (suppressing) interactions, respectively.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Cited by

Sorted by citations

See all 252

Related

See all

Metadata

Authors
Li, J.-Q., Tan, L., & Yu, J.-T.
Affiliations
Qingdao University (CN)
Corresponding author
  • Tan, Lan
  • Yu, Jin-Tai
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2014-11-12
Volume
9
Issue
1
Pages
47-47
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/1750-1326-9-47
PMC
PMC4246469
OpenAlex
W2145005920
Cited by
249
References
127
Citations by year
2026: 9 · 2025: 18 · 2024: 24 · 2023: 29 · 2022: 27 · 2021: 15 · 2020: 28 · 2019: 30 · 2018: 30 · 2017: 17 · 2016: 12 · 2015: 10
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81371406, ZR2011HZ001, 81171209, 81471309, ZR2010HQ004)
  • Natural Science Foundation of Shandong Province (ZR2011HZ001, ZR2010HQ004)
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
LRRK2, Parkinson's disease, leucine-rich repeat kinase 2, LRRK2 mutations, alpha-synuclein, tau protein, neuroinflammation, oxidative stress, mitochondrial dysfunction, synaptic dysfunction, autophagy-lysosome pathway, therapeutic target
MeSH terms
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Animals, Humans, Protein Serine-Threonine Kinases, Parkinsonian Disorders

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review