Evidence map›Paper›PMID 25251388›Full record

ReviewJournal of neurochemistry2014

LRRK2 pathobiology in Parkinson's disease.

Ian Martin, Jungwoo Wren Kim, Valina L Dawson, Ted M Dawson

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

Review in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Mitochondrial Dysfunction in Genetic and Non-Genetic Parkinson's Disease.International journal of molecular sciences · 2025
    Review
  10. Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.CNS & neurological disorders drug targets · 2025
    Review
  11. Review
  12. Metabolic Parkinson's disease.Frontiers in aging neuroscience · 2025
    Review
  13. Article
  14. Review
  15. Mass spectrometry-based proteomics for biomarker discovery in theNeuroprotection (Chichester, England) · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

34 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

4 authors at 3 institutions in 1 country.

Ian MartinNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jungwoo Wren Kim
Valina L Dawson
Ted M Dawson
Johns Hopkins University · USJohns Hopkins Medicine · USOrthopaedic Research Foundation · US

Funding

Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KO, HANSEOK · 1998 to 2019
$38.8M
NINDS NIH HHS NS38377NINDS NIH HHS P50 NS038377
6 · The paper itself

Abstract

Mutations in the catalytic Roc-COR and kinase domains of leucine-rich repeat kinase 2 (LRRK2) are a common cause of familial Parkinson's disease (PD). LRRK2 mutations cause PD with age-related penetrance and clinical features identical to late-onset sporadic PD. Biochemical studies support an increase in LRRK2 kinase activity and a decrease in GTPase activity for kinase domain and Roc-COR mutations, respectively. Strong evidence exists that LRRK2 toxicity is kinase dependent leading to extensive efforts to identify selective and brain-permeable LRRK2 kinase inhibitors for clinical development. Cell and animal models of PD indicate that LRRK2 mutations affect vesicular trafficking, autophagy, protein synthesis, and cytoskeletal function. Although some of these biological functions are affected consistently by most disease-linked mutations, others are not and it remains currently unclear how mutations that produce variable effects on LRRK2 biochemistry and function all commonly result in the degeneration and death of dopamine neurons. LRRK2 is typically present in Lewy bodies and its toxicity in mammalian models appears to be dependent on the presence of α-synuclein, which is elevated in human iPS-derived dopamine neurons from patients harboring LRRK2 mutations. Here, we summarize biochemical and functional studies of LRRK2 and its mutations and focus on aberrant vesicular trafficking and protein synthesis as two leading mechanisms underlying LRRK2-linked disease.

Indexed as

GTP PhosphohydrolasesHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MutationParkinson DiseaseProtein Serine-Threonine KinasesProtein TransportSynucleinsGTP PhosphohydrolasesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Serine-Threonine KinasesSynucleinsalpha-synucleinGTPasekinaseneurodegenerationprotein translationRps15

Identifiers

PMID25251388
PMCPMC4237709
OpenAlexW2037897058

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.