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Taurine prevents the neurotoxicity of β‐amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders
Author(s) -
Louzada Paulo Roberto,
Lima Andréa C. Paula,
MendoncaSilva Dayde L.,
Noël Francois,
De Mello Fernando G.,
Ferreira Sérgio T.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0739com
Subject(s) - excitotoxicity , glutamate receptor , neurotoxicity , neuroprotection , glutamatergic , gabaergic , kainic acid , receptor , neuroscience , chemistry , pharmacology , biology , inhibitory postsynaptic potential , medicine , biochemistry , toxicity
Alzheimer's disease (AD) and several other neurological disorders have been linked to the overactivation of glutamatergic transmission and exci‐totoxicity as a common pathway of neuronal injury. The β‐amyloid peptide (Aβ) is centrally related to the pathogenesis of AD, and previous reports have demon¬strated that the blockade of glutamate receptors pre¬vents Aβ‐induced neuronal death. We show that tau¬rine, a β‐amino acid found at high concentrations in the brain, protects chick retinal neurons in culture against the neurotoxicity of Aβ and glutamate receptor ago¬nists. The protective effect of taurine is not mediated by interaction with glutamate receptors, as demon¬strated by binding studies using radiolabeled glutamate receptor ligands. The neuroprotective action of taurine is blocked by picrotoxin, an antagonist of GABA A receptors. GABA and the GABA A receptor agonists phenobarbital and melatonin also protect neurons against Aβ ‐induced neurotoxicity. These results suggest that activation of GABA receptors decreases neuronal vulnerability to excitotoxic damage and that pharmaco¬logical manipulation of the excitatory and inhibitory neurotransmitter tonus may protect neurons against a variety of insults. GABAergic transmission may repre¬sent a promising target for the treatment of AD and other neurological disorders in which excitotoxicity plays a relevant role.—Louzada, P. R., Lima, A. C. P., Mendonca‐Silva, D. L., Noël, F., de Mello, F. G., Ferreira, S. T. Taurine prevents the neurotoxicity of β‐amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alz¬heimer's disease and other neurological disorders.