652. Adeno-Associated Vector Delivery of Gutamate Transporters in an ALS Mouse Model

Abstract

Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disease characterized by a selective loss of motor neurons in the motor cortex, brainstem and spinal cord. The cause of motor neuron degeneration remains largely unknown and there is to date no effective therapy. Glutamate is the main excitatory neurotransmitter in the central nervous system (CNS). Paradoxically, overactivation of glutamatergic neurons and extracellular accumulation of glutamate contributes to neuronal cell death observed in acute and chronic CNS insults, including ALS. The increased glutamate levels surrounding vulnerable motor neurons result from a pronounced loss of the excitatory amino acid transporter 2 (EAAT2) in affected ALS brain regions. EAAT2 (called GLT1 in rodents) is the predominant glutamate transporter in the CNS and is present on astrocytes. Loss of GLT-1 protein and function also occurs in mouse and rat ALS models.