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

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Abstract
Alzheimer’s disease (AD) and several other neurological disorders have been linked to the overactivation of glutamatergic transmission and excitotoxicity as a common pathway of neuronal injury. The β-amyloid peptide (Aβ) is centrally related to the pathogenesis of AD, and previous reports have demonstrated that the blockade of glutamate receptors prevents Aβ–induced neuronal death. We show that taurine, 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 agonists. The protective effect of taurine is not mediated by interaction with glutamate receptors, as demonstrated by binding studies using radiolabeled glutamate receptor ligands. The neuroprotective action of taurine is blocked by picrotoxin, an antagonist of GABAA receptors. GABA and the GABAA 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 pharmacological manipulation of the excitatory and inhibitory neurotransmitter tonus may protect neurons against a variety of insults. GABAergic transmission may represent 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., Mendonça-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 Alzheimer’s disease and other neurological disorders.
Funding Information
  • John Simon Guggenheim Memorial Foundation
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

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