UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Dopamine induced neurodegeneration in a PINK1 model of Parkinson's disease.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Gandhi S, Vaarmann A, Yao Z, Duchen MR, Wood NW, Abramov AY
  • Publication date:
    2012
  • Pagination:
    e37564, ?
  • Journal:
    PLoS One
  • Volume:
    7
  • Issue:
    5
  • Status:
    Published
  • Country:
    United States
  • PII:
    PONE-D-11-22984
  • Language:
    eng
  • Keywords:
    Animals, Apoptosis, Calcium, Disease Models, Animal, Dopamine, Dopaminergic Neurons, Humans, Membrane Potential, Mitochondrial, Mice, Mice, Knockout, Mitochondria, Mitochondrial Membrane Transport Proteins, Parkinson Disease, Protein Kinases, Reactive Oxygen Species
Abstract
BACKGROUND: Parkinson's disease is a common neurodegenerative disease characterised by progressive loss of dopaminergic neurons, leading to dopamine depletion in the striatum. Mutations in the PINK1 gene cause an autosomal recessive form of Parkinson's disease. Loss of PINK1 function causes mitochondrial dysfunction, increased reactive oxygen species production and calcium dysregulation, which increases susceptibility to neuronal death in Parkinson's disease. The basis of neuronal vulnerability to dopamine in Parkinson's disease is not well understood. METHODOLOGY: We investigated the mechanism of dopamine induced cell death in transgenic PINK1 knockout mouse neurons. We show that dopamine results in mitochondrial depolarisation caused by mitochondrial permeability transition pore (mPTP) opening. Dopamine-induced mPTP opening is dependent on a complex of reactive oxygen species production and calcium signalling. Dopamine-induced mPTP opening, and dopamine-induced cell death, could be prevented by inhibition of reactive oxygen species production, by provision of respiratory chain substrates, and by alteration in calcium signalling. CONCLUSIONS: These data demonstrate the mechanism of dopamine toxicity in PINK1 deficient neurons, and suggest potential therapeutic strategies for neuroprotection in Parkinson's disease.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Clinical and Movement Neurosciences
Author
Cell & Developmental Biology
Author
Clinical and Movement Neurosciences
Author
Clinical and Movement Neurosciences
Author
Clinical and Movement Neurosciences
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by