Neurochemical Research

, Volume 24, Issue 11, pp 1423–1430

Neurotoxic and Synaptic Effects of Okadaic Acid, an Inhibitor of Protein Phosphatases

  • Ricardo Tapia
  • Fernando Peña
  • Clorinda Arias
Article

DOI: 10.1023/A:1022588808260

Cite this article as:
Tapia, R., Peña, F. & Arias, C. Neurochem Res (1999) 24: 1423. doi:10.1023/A:1022588808260

Abstract

Protein phosphorylation and dephosphorylation reactions, catalyzed by kinases and phosphatases, are involved in the regulation of a wide variety of physiological processes. In the nervous system, such reactions seem to modulate the function of several proteins crucial in synaptic transmission, including voltage-gated and ligand-gated channels, neurotransmitter release, and neurotransmitter transporters. On the other hand, hyperphosphorylation of certain cytoskeletal proteins or receptors may lead to neuronal death. In the present work we review the neurotoxic effect of okadaic acid (OKA), a potent and specific inhibitor of the serine/threonine protein phosphatases 1 and 2A, as well as its action on synaptic function. We analyze recent findings demonstrating that the microinjection of OKA in rat hippocampus induces neuronal stress, hyperexcitation and neurodegeneration, and discuss their possible relationships to alterations of protein phosphorylation-dephosphorylation observed in Alzheimer's disease brain. These results suggest that protein hyperphosphorylation due to inhibition of phosphatases in vivo induces neuronal stress and subsequent neurodegeneration.

Protein phosphatasesokadaic acidneurodegenerationhippocampusALZ-50heat-shock proteins

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Ricardo Tapia
    • 1
  • Fernando Peña
    • 1
  • Clorinda Arias
    • 2
  1. 1.Departamento de Neurociencias, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMéxico, D.F.México
  2. 2.Departamento de Biología Celular, Instituto de Investigaciones BiomédicasUniversidad National Autónoma de MéxicoMéxico, D.F.México