Critical Reviews™ in Neurobiology

ISSN for PRINT: 0892-0915

For Online Access

Best Paper Award Selection - Editorial Board Site

2004, Volume16

Issue 1&2

194 pages

DOI: 10.1615/CritRevNeurobiol.v16.i12

Issue price - $252.00

Gabriel A. de Erausquin
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA

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 GluR_AMPA 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.

DOI: 10.1615/CritRevNeurobiol.v16.i12.120 Download article, 107-119 pages

Article price - $35.00

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