Evidence map›Paper›PMID 32169097›Full record

ReviewMolecular neurodegeneration2020

PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson's disease.

Preston Ge, Valina L Dawson, Ted M Dawson

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

Review in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
279citing papers in PubMed, 2 pooled it
23.8field-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

279 citing papers in PubMed, 2 syntheses or guidelines pooled it, 469 citations in OpenAlex.

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219 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 2 institutions in 2 countries.

Preston GeNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Department of Physiology, Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 733 North Broadway, Suite 731, Baltimore, MD, 21205, USA.
Valina L DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Department of Physiology, Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 733 North Broadway, Suite 731, Baltimore, MD, 21205, USA. vdawson@jhmi.edu.
Ted M DawsonNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Department of Physiology, Solomon H. Snyder Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 733 North Broadway, Suite 731, Baltimore, MD, 21205, USA. tdawson@jhmi.edu.ORCID 0000-0002-6459-0893
Johns Hopkins University · USHarvard University · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753
6 · The paper itself

Abstract

That certain cell types in the central nervous system are more likely to undergo neurodegeneration in Parkinson's disease is a widely appreciated but poorly understood phenomenon. Many vulnerable subpopulations, including dopamine neurons in the substantia nigra pars compacta, have a shared phenotype of large, widely distributed axonal networks, dense synaptic connections, and high basal levels of neural activity. These features come at substantial bioenergetic cost, suggesting that these neurons experience a high degree of mitochondrial stress. In such a context, mechanisms of mitochondrial quality control play an especially important role in maintaining neuronal survival. In this review, we focus on understanding the unique challenges faced by the mitochondria in neurons vulnerable to neurodegeneration in Parkinson's and summarize evidence that mitochondrial dysfunction contributes to disease pathogenesis and to cell death in these subpopulations. We then review mechanisms of mitochondrial quality control mediated by activation of PINK1 and Parkin, two genes that carry mutations associated with autosomal recessive Parkinson's disease. We conclude by pinpointing critical gaps in our knowledge of PINK1 and Parkin function, and propose that understanding the connection between the mechanisms of sporadic Parkinson's and defects in mitochondrial quality control will lead us to greater insights into the question of selective vulnerability.

Indexed as

AnimalsEnergy MetabolismHumansMitochondriaNerve DegenerationNeuronsParkinson DiseaseProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein Ligasesparkin proteinProtein KinasesPTEN-Induced Putative KinaseUbiquitin-Protein LigasesMitochondriaMitophagyParkinParkinson diseasePINK1Selective vulnerabilitySubstantia nigra

Identifiers

PMID32169097
PMCPMC7071653
OpenAlexW3011802680

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.