Received for publication August 22, 2007.
Revised August 28, 2007.
Accepted for publication August 28, 2007.

Parawixin1: a spider toxin opening new avenues for glutamate transporter pharmacology (Relates to article by Fontana, et al., Fast Forward 23 July 2007)

Abstract

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After release from glutamatergic nerve terminals, glial and neuronal glutamate transporters remove glutamate from the synaptic cleft to terminate synaptic transmission and to prevent neuronal damage by excessive glutamate receptor activation. In this issue of Molecular Pharmacology, Fontana et al. study the action of a venom compound, Parawixin1, on excitatory amino acid transporters (EAATs). They demonstrate that this agent selectively affects a glial glutamate transporter, EAAT2, by specifically increasing one particular step of the glutamate uptake cycle. Disturbed glutamate homeostasis appears to be a pathogenetic factor in several neurodegenerative disorders. Since EAAT2 is a key player in determining the extracellular glutamate concentration in the mammalian brain, drugs targeting this protein could prevent glutamate excitotoxicity without blocking glutamatergic transmission. Its specificity and selectivity makes Parawixin1 a perfect starting point to design small molecules for the treatment of pathological conditions caused by alterations of glutamate homeostasis.

Key words: Amino Acid, Ischemia/Reperfusion, Synaptic plasticity