Transactivation of cell death signals by glutamate transmission in dopaminergic neurons

Research output: Contribution to journalReview article

4 Scopus citations

Abstract

The intrinsic susceptibility of dopaminergic neurons underlies the pathophysiology of Parkinson's disease and is possibly related to developmental injury in schizophrenia. However, the molecular substrates for this susceptibility are not well understood. We review the evidence of selective susceptibility of dopaminergic neurons to excessive glutamate receptor stimulation and discuss the molecular pathways that differentiate between physiological and pathological signaling leading to this particular form of neuronal death. In vitro as well as in vivo, activation of GluRAMPA causes concentration-dependent, severe pruning of neurites and selective death of dopaminergic neurons. In primary cultures of mesencephalon, this form of injury is mediated through release of calcium from intracellular stores (CICR), leading to loss of calcium homeostasis, oxidative stress, and activation of the transcription factor NFκB and the cell death protein p53. Post-translational modification of p53 may be an important target for neuroprotection in Parkinson's disease and perhaps in prevention of other neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)107-119
Number of pages13
JournalCritical Reviews in Neurobiology
Volume16
Issue number1-2
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Dopaminergic neurons
  • Excitotoxicity
  • Neuronal death
  • Nuclear factor kappa B (NFκB)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Clinical Neurology
  • Physiology (medical)

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