Rocephin in Mouse Mouse Model of ALS!!!!!!!!!!!

CaliforniaLyme · medicine forum Guru Joined: 28 Apr 2005 Posts: 2066

This deserved its own thread!!!!!
****************************************

1: Nature. 2005 Jan 6;433(7021):73-7. Related Articles, Links

Beta-lactam antibiotics offer neuroprotection by increasing glutamate
transporter expression.

Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, Jin
L, Dykes Hoberg M, Vidensky S, Chung DS, Toan SV, Bruijn LI, Su ZZ,
Gupta P, Fisher PB.

Department of Neurology, Johns Hopkins University, Baltimore, Maryland
21287, USA. jrothste@jhmi.edu

Glutamate is the principal excitatory neurotransmitter in the nervous
system. Inactivation of synaptic glutamate is handled by the glutamate
transporter GLT1 (also known as EAAT2; refs 1, 2), the physiologically
dominant astroglial protein. In spite of its critical importance in
normal and abnormal synaptic activity, no practical pharmaceutical can
positively modulate this protein. Animal studies show that the protein
is important for normal excitatory synaptic transmission, while its
dysfunction is implicated in acute and chronic neurological disorders,
including amyotrophic lateral sclerosis (ALS), stroke, brain tumours
and epilepsy. Using a blinded screen of 1,040 FDA-approved drugs and
nutritionals, we discovered that many beta-lactam antibiotics are
potent stimulators of GLT1 expression. Furthermore, this action appears
to be mediated through increased transcription of the GLT1 gene.
beta-Lactams and various semi-synthetic derivatives are potent
antibiotics that act to inhibit bacterial synthetic pathways. When
delivered to animals, the beta-lactam ceftriaxone increased both brain
expression of GLT1 and its biochemical and functional activity.
Glutamate transporters are important in preventing glutamate
neurotoxicity. Ceftriaxone was neuroprotective in vitro when used in
models of ischaemic injury and motor neuron degeneration, both based in
part on glutamate toxicity. When used in an animal model of the fatal
disease ALS, the drug delayed loss of neurons and muscle strength, and
increased mouse survival. Thus these studies provide a class of
potential neurotherapeutics that act to modulate the expression of
glutamate neurotransmitter transporters via gene activation.

PMID: 15635412 [PubMed - indexed for MEDLINE]

Google