Cited by 58Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingAdvanced Proteomics Techniques and Applications

Quantitative expression proteomics and phosphoproteomics profile of brain from PINK1 knockout mice: insights into mechanisms of familial Parkinson's disease

Triplett, Judy C., Zhang, Zhaoshu, Sultana, Rukhsana, Cai, Jian, Klein, Jon B., Büeler, Hansruedi, Butterfield, David Allan·2015·Journal of Neurochemistry

Abstract

Parkinson's disease (PD) is an age-related, neurodegenerative motor disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and presence of α-synuclein-containing protein aggregates. Mutations in the mitochondrial Ser/Thr kinase PTEN-induced kinase 1 (PINK1) are associated with an autosomal recessive familial form of early-onset PD. Recent studies have suggested that PINK1 plays important neuroprotective roles against mitochondrial dysfunction by phosphorylating and recruiting Parkin, a cytosolic E3 ubiquitin ligase, to facilitate elimination of damaged mitochondria via autophagy-lysosomal pathways. Loss of PINK1 in cells and animals leads to various mitochondrial impairments and oxidative stress, culminating in dopaminergic neuronal death in humans. Using a 2-D polyacrylamide gel electrophoresis proteomics approach, the differences in expressed brain proteome and phosphoproteome between 6-month-old PINK1-deficient mice and wild-type mice were identified. The observed changes in the brain proteome and phosphoproteome of mice lacking PINK1 suggest that defects in signaling networks, energy metabolism, cellular proteostasis, and neuronal structure and plasticity are involved in the pathogenesis of familial PD. Mutations in PINK1 are associated with an early-onset form of Parkinson's disease (PD). This study examines changes in the proteome and phosphoproteome of the PINK1 knockout mouse brain. Alterations were noted in several key proteins associated with: increased oxidative stress, aberrant cellular signaling, altered neuronal structure, decreased synaptic plasticity, reduced neurotransmission, diminished proteostasis networks, and altered metabolism. 14-3-3ε, 14-3-3 protein epsilon; 3-PGDH, phosphoglycerate dehydrogenase; ALDOA, aldolase A; APT1, acyl-protein thioesterase 1; CaM, calmodulin; CBR3, carbonyl reductase [NADPH] 3; ENO2, gamma-enolase; HPRT, hypoxanthine-guanine phosphoribosyltransferase; HSP70, heat-shock-related 70 kDa protein 2; IDHc, cytoplasmic isocitrate dehydrogenase [NADP+]; MAPK1, mitogen-activated protein kinase 1; MEK1, MAP kinase kinase 1; MDHc, cytoplasmic malate dehydrogenase; NFM, neurofilament medium polypeptide; NSF, N-ethylmaleimide-sensitive fusion protein; PHB, prohibitin; PINK1, PTEN-induced putative kinase 1; PPIaseA, peptidyl-prolyl cis-trans isomerase A; PSA2, proteasome subunit alpha type-2; TK, transketolase; VDAC-2, voltage-dependent anion-selective channel protein 2.

Integrity signals

Registry

Crossref · 10.1111/jnc.13039

Cites

136 of 136 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Reduced mitophagy via Pink1/Parkin-regulated ubiquitination in aged neurons contributes to greater ROS accumulation.

    “Reduced mitophagy associated Pink1- and Parkin-regulated ubiquitination of the outer mitochondrial membrane of damaged mitochondria in aged neurons (79, 99, 140) contribute to a greater accumulation of ROS (81).”

    From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [140]

Cites

Flagged first, then by citations

2 of the 138 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Triplett, J. C., Zhang, Z., Sultana, R., Cai, J., Klein, J. B., Büeler, H., & Butterfield, D. A.
Affiliations
  • University of Kentucky (US)
  • Department of Chemistry University of Kentucky Lexington Kentucky USA
  • University of Louisville (US)
Corresponding author
Butterfield, David Allan
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2015-03
Volume
133
Issue
5
Pages
750-765
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W1974069592
Cited by
58
References
138
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 10 · 2018: 2 · 2017: 7 · 2016: 6 · 2015: 6
FWCI
4.94
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of Kentucky Research Challenge Trust Fund
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
Parkinson's disease, PINK1, Parkin, PINK1 knockout mice, brain proteome, phosphoproteome, mitochondrial dysfunction, oxidative stress, dopaminergic neurons, synaptic plasticity, energy metabolism, proteostasis, MAPK signaling, 14-3-3 proteins, mitophagy, neurodegeneration, protein phosphorylation
MeSH terms
Prohibitins, PTEN-Induced Putative Kinase, Animals, Brain Chemistry, Male, Parkinson Disease, Peptides, Phosphoproteins, Protein Kinases, Trypsin, Blotting, Western, Mice, Knockout, Proteomics, Proteasome Endopeptidase Complex, Immunoprecipitation, Mice

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