Riluzole neuroprotection in a Parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation.

Background: Riluzole is a neuroprotective drug used in the treatment of motor neurone disease. Recent evidence suggests that riluzole can up-regulate the expression and activity of the astrocyte glutamate transporter, GLT-1. Given that regulation of glutamate transport is predicted to be neuroprotective in Parkinson's disease, we tested the effect of riluzole in parkinsonian rats which had received a unilateral 6-hydroxydopamine injection into the median forebrain bundle.

Riluzole elevates GLT-1 activity and levels in striatal astrocytes.

Drugs which upregulate astrocyte glutamate transport may be useful neuroprotective compounds by preventing excitotoxicity. We set up a new system to identify potential neuroprotective drugs which act through GLT-1. Primary mouse striatal astrocytes grown in the presence of the growth-factor supplement G5 express high levels of the functional glutamate transporter, GLT-1 (also known as EAAT2) as assessed by Western blotting and ³H-glutamate uptake assay, and levels decline following growth factor withdrawal.

Significant correction of pathology in brains of twitcher mice following injection of genetically modified mouse neural progenitor cells.

Krabbe disease or globoid cell leukodystrophy is an autosomal recessive disorder resulting from mutations in the galactocerebrosidase (GALC) gene. These mutations lead to deficient GALC activity, storage of substrates of the enzyme, including psychosine, death to oligodendrocytes, decreased myelination, production of globoid cells and eventually death to the individual. While most affected individuals are infants, late-onset forms are also recognized.

Increased CD4 and CCR5 expression and human immunodeficiency virus type 1 entry in CD40 ligand-stimulated macrophages.

The effects of a soluble trimeric CD40 ligand (CD40L) agonist on the expression of CD4 and CCR5 and on human immunodeficiency virus (HIV) type 1 entry into and replication in human macrophages were investigated. CD40L increased the number of CD4 and CCR5 antibody-binding sites and the percentage of CD4- and CCR5-expressing cells. Infection of CD40L-stimulated macrophages with HIV-1 resulted in a marked increase of viral DNA with respect to controls, as demonstrated by polymerase chain reaction assay.