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

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PINK1 protein in normal human brain and Parkinson's disease

Gandhi, S.·2006·Brain

DOI 10.1093/brain/awl114

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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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Authors: Gandhi, S.
Affiliations: UCL Queen Square Institute of Neurology (GB)
Corresponding author: Gandhi, S.
ORCID: Gandhi, S.
Venue: Brain
Publisher: Oxford University Press (OUP)
Published: 2006-07-01
Volume: 129
Issue: 7
Pages: 1720-1731
ISSN: 0006-8950 (ISSN-L)
1460-2156
DOI: 10.1093/brain/awl114
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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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PINK1 protein in normal human brain and Parkinson's disease

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