The excitatory amino acid transporter 2 (EAAT2) plays
a key role
in the clearance and recycling of glutamate - the major excitatory
neurotransmitter in the mammalian brain. EAAT2 loss/dysfunction triggers
a cascade of neurodegenerative events, comprising glutamatergic excitotoxicity
and neuronal death. Nevertheless, our current knowledge regarding
EAAT2 in neurodegenerative diseases, such as amyotrophic lateral sclerosis
(ALS) and Alzheimer’s disease (AD), is restricted to post-mortem
analysis of brain tissue and experimental models. Thus, detecting
EAAT2 in the living human brain might be crucial to improve diagnosis/therapy
for ALS and AD. This perspective article describes the role of EAAT2
in physio/pathological processes and provides a structure–activity
relationship of EAAT2-binders, bringing two perspectives: therapy
(activators) and diagnosis (molecular imaging tools).