Cited by 342Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeurological diseases and metabolism

PINK1 protein in normal human brain and Parkinson's disease

Gandhi, S.·2006·Brain

Abstract

Parkinson's disease is a common incurable neurodegenerative disease whose molecular aetiology remains unclear. The identification of Mendelian genes causing rare familial forms of Parkinson's disease has revealed novel proteins and pathways that are likely to be relevant in the pathogenesis of sporadic Parkinson's disease. Recently, mutations in a novel gene, PINK1, encoding a 581 amino acid protein with both mitochondrial targeting and serine/threonine kinase domains, were identified as a cause of autosomal recessive parkinsonism. This provided important evidence for the role of the mitochondrial dysfunction and kinase pathways in neurodegeneration. In this study, we report the first characterization of the PINK1 protein in normal human and sporadic Parkinson's brains, in addition to Parkinson's cases with heterozygous PINK1 mutations. The possible role of the PINK1 protein was also assessed in a number of neurodegenerative diseases characterized by proteinaceous inclusions. For these studies, rabbit polyclonal antibodies were raised against two peptide sequences within the N-terminal hydrophilic loops of PINK1 protein. Using immunohistochemistry and western blotting we were able to demonstrate that PINK1 is a ubiquitous protein expressed throughout the human brain and it is found in all cell types showing a punctate cytoplasmic staining pattern consistent with mitochondrial localization. Fractionation studies of human and rat brain confirm that PINK1 is localized to the mit…

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Crossref · 10.1093/brain/awl114

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Authors
Gandhi, S.
Affiliations
UCL Queen Square Institute of Neurology (GB)
Corresponding author
Gandhi, S.
Venue
Brain
Published
2006-07-01
Volume
129
Issue
7
Pages
1720-1731
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
OpenAlex
W2131641631
Cited by
342
References
49
Citations by year
2026: 6 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 8 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 9 · 2017: 10 · 2016: 14 · 2015: 12 · 2014: 17 · 2013: 22 · 2012: 22
FWCI
24.12
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust
  • Parkinson's UK (G-4062)
  • Cotton Research and Development Corporation
  • Medical Research Council
  • Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology,University College London
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
PINK1, Parkinson's disease, sporadic Parkinson's disease, mitochondrial dysfunction, Lewy bodies, mitochondrial localization, neurodegeneration, autosomal recessive parkinsonism, neurofibrillary tangles, alpha-synuclein inclusions, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, Alzheimer's disease, serine/threonine kinase
MeSH terms
PTEN-Induced Putative Kinase, Alzheimer Disease, Animals, Brain, Carbonates, Female, Heterozygote, Humans, Immunoenzyme Techniques, Male, Middle Aged, Mitochondria, Mutation, Parkinson Disease, Protein Kinases, Submitochondrial Particles, Rats, Wistar, Multiple System Atrophy, Lewy Body Disease, Mitochondrial Membranes, Rats

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