The excitatory amino acid transporters (EAATs) are transmembrane proteins responsible for the uptake of (S)-glutamate from the synaptic cleft. To date, five subtypes EAAT1-5 have been identified for which selective inhibitors have been discovered for EAAT1 and EAAT2. By screening of a commercially available compound library consisting of 4,000 compounds, N-acyl-N-phenylpiperazine analog (±)- ex...

To maintain reliable signal transmission across a synapse, free synaptic neurotransmitters must be removed from the cleft in a timely manner. In the first visual synapse, this critical task is mainly undertaken by glutamate transporters (EAATs). Here we study the differential roles of the EAAT1, EAAT2 and EAAT5 subtypes in glutamate (GLU) uptake at the photoreceptor-to-depolarizing bipolar cell...

BACKGROUND/AIMS Klotho, a transmembrane protein expressed in chorioid plexus of the brain, kidney, and several other tissues, is required for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. At least in part by exerting β-glucuronidase activity, soluble klotho regulates several i...

Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to e...

INTRODUCTION Growth factors, cytokines, sex steroid hormones and glucocorticoids have differential and complex effects on skeletal metabolism. Recently, the presence of the glutamatergic (Glu) system in bone cells has provided new evidence for its possible role in bone physiology. Consequently, we have investigated the regulation of certain components of the Glu system by glucocorticoids in MG-...

BACKGROUND Episodic ataxia (EA) is variably associated with additional neurologic symptoms. At least 4 genes have been implicated. Recently, a mutation in the SLC1A3 gene encoding the glutamate transporter EAAT1 was identified in a patient with severe episodic and progressive ataxia, seizures, alternating hemiplegia, and migraine headache. The mutant EAAT1 showed severely reduced uptake of glut...

Glutamate transport is coupled to the co-transport of 3 Na(+) and 1 H(+) followed by the counter-transport of 1 K(+). In addition, glutamate and Na(+) binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water pe...

Chronic exposure to inorganic arsenic severely damages the central nervous system (CNS). Glutamate (GLU) is the major excitatory amino acid and is highly neurotoxic when levels in the synaptic cleft are not properly regulated by a family of Na⁺-dependent excitatory amino acid transporters. Within the cerebellum, the activity of the Bergmann glia Na⁺-dependent GLU/aspartate transporter (GLAST) e...

Transient focal cerebral ischemia leads to extensive excitotoxic glial damage in the subcortical white matter. Efficient reuptake of released glutamate is essential for preventing glutamate receptor overstimulation and neuronal and glial death. The present study evaluates the expression of the main glutamate transporters (EAAT1, EAAT2, and EAAT3) in subcortical white matter of the rat after tra...

Leber hereditary optic neuropathy (LHON) is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy which is caused by point mutations in the mitochondrial genome (mtDNA). Three pathogenic mutations (positions 11778/ND4, 3460/ND1 and 14484/ND6) account for the majority of LHON cases and they affect genes that encode for different subunits of mitochondrial comp...