Ceftriaxone protects against the neurotoxicity of human immunodeficiency virus proteins.
Human immunodeficiency virus (HIV) proteins Tat and gp120 have been implicated in the pathogenesis of HIV dementia by various mechanisms, including down-regulation of excitatory amino acid transporter-2 (EAAT2), which is responsible for inactivation of synaptic glutamate. Recent work indicates that beta-lactam antibiotics are potent stimulators of EAAT2 expression. The authors treated mixed human fetal neuronal cultures with recombinant gp120 or Tat, in the presence or absence of ceftriaxone, and determined neurotoxicity by measuring mitochondrial membrane potential and neuronal cell death. Ceftriaxone produced dose-dependent attenuation of the neurotoxicity and neuronal cell death caused by both viral proteins. This study demonstrates that this class of drugs may have therapeutic efficacy in HIV dementia.
Rumbaugh
Jeffrey A
JA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jrumbaug@jhmi.edu
Li
Guanhan
G
Rothstein
Jeffrey
J
Nath
Avindra
A
D002443:Ceftriaxone / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015696:Gene Products, tat / Q000633:toxicity*; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011994:Recombinant Proteins / Q000633:toxicity
D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D002443:Ceftriaxone