Evidence map›Paper›PMID 31287913›Full record

ReviewJournal of neurochemistry2019

Role of the endolysosomal system in Parkinson's disease.

D J Vidyadhara, John E Lee, Sreeganga S Chandra

Open access · bronzeAbstract readReview
In one paragraph

Review in Journal of neurochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
12.7field-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

79 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026
    Review
  9. Article
  10. Review
  11. Article
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19 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.

D J VidyadharaDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-0974-0307
John E LeeDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Sreeganga S ChandraDepartment of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
Yale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Role of Glucosylsphingosine in Parkinson Disease and Dementia with Lewy BodiesRF1NS110354 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2019 to 2022
$2.5M
Roles of the CSPalpha Chaperone Complex in Presynaptic Maintenance and ANCLR01NS083846 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2014 to 2018
$2.2M
The Physiological Functions of SynucleinsR01NS064963 · NINDS · YALE UNIVERSITY · PI CHANDRA, SREEGANGA S · 2010 to 2014
$1.6M
Elucidating GBA-linked Parkinson's disease and Dementia with Lewy BodiesR01NS110354 · NINDS · YALE UNIVERSITY · PI Sreeganga S Chandra · 2026 to 2026
$654k
NCATS NIH HHS UL1 TR001863NINDS NIH HHS R01 NS064963NINDS NIH HHS R01 NS083846NINDS NIH HHS R01 NS110354NINDS NIH HHS RF1 NS110354
6 · The paper itself

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, affecting 1-1.5% of the total population. While progress has been made in understanding the neurodegenerative mechanisms that lead to cell death in late stages of PD, mechanisms for early, causal pathogenic events are still elusive. Recent developments in PD genetics increasingly point at endolysosomal (E-L) system dysfunction as the early pathomechanism and key pathway affected in PD. Clathrin-mediated synaptic endocytosis, an integral part of the neuronal E-L system, is probably the main early target as evident in auxilin, RME-8, and synaptojanin-1 mutations that cause PD. Autophagy, another important pathway in the E-L system, is crucial in maintaining proteostasis and a healthy mitochondrial pool, especially in neurons considering their inability to divide and requirement to function an entire life-time. PINK1 and Parkin mutations severely perturb autophagy of dysfunctional mitochondria (mitophagy), both in the cell body and synaptic terminals of dopaminergic neurons, leading to PD. Endolysosomal sorting and trafficking is also crucial, which is complex in multi-compartmentalized neurons. VPS35 and VPS13C mutations noted in PD target these mechanisms. Mutations in GBA comprise the most common risk factor for PD and initiate pathology by compromising lysosomal function. This is also the case for ATP13A2 mutations. Interestingly, α-synuclein and LRRK2, key proteins involved in PD, function in different steps of the E-L pathway and target their components to induce disease pathogenesis. In this review, we discuss these E-L system genes that are linked to PD and how their dysfunction results in PD pathogenesis. This article is part of the Special Issue "Synuclein".

Indexed as

AutophagyAxonsCorpus StriatumEndocytosisEndosomesForecastingGenetic Association StudiesHumansLysosomesMembrane FusionMitophagyMutationNerve Tissue ProteinsParkinson DiseaseRisk FactorsSubstantia NigraNerve Tissue ProteinsAutophagyClathrin-mediated endocytosisLRRK2LysosomesRetromer complexα-Synuclein

Identifiers

PMID31287913
PMCPMC6707858
OpenAlexW2960681055

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.