Flupirtine Partially Prevents Neuronal Injury Induced by Prion Protein Fragment and Lead Acetate

Inhibitors of Brain Phospholipase A2Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

“…PrP sc and PrP106-126, a neurotoxic prion peptide, are known to stimulate NMDA receptors. This stimulation is blocked by MK-801, memantine, and flupirtine (Muller et al, 1993;Perovic et al, 1995;Peyrin et al, 1999). PrP106-126 peptide-mediated stimulation of the NMDA receptor is accompanied with the release of arachidonic acid in cerebellar granule neurons, suggesting the association of PLA 2 isoforms in the pathogenesis of prion diseases ).…”

Inhibition of IL-1β Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt–Jakob Disease

“…(v) CJD prions (Ratte et al, 2008), and when PrP Sc , or the PrP Sc -like PrP106-126 peptide, was exogenously 88 presented to cultured neurons, NMDAR antagonists blocked the resulting neurotoxicity (Muller et al, 1993; 89 Perovic et al, 1995;Brown et al, 1997;Resenberger et al, 2011;Thellung et al, 2012).…”

Suppression of PrPSc- and HIV-1 gp120 induced neuronal cell death by sulfated colominic acid

“…Previously we demonstrated that neuronal cell death induced by PrP Sc or HIV-1 gp120 can be prevented by the NMDA receptor antagonists, memantine and MK-801 (Mu È ller et al, 1992Ushijima et al, 1993;Perovic et al, 1995). This result indicates that PrP Sc and gp120 activate NMDA receptors, but the underlying mechanism is poorly understood.…”

“…This deleterious protein is thought to be formed by conversion of the putative a-helices of the normal cellular prion protein (PrP C ) into b-sheets (Gasset et al, 1992). The mechanism underlying the neurotoxic effect of PrP Sc and of its peptide fragment, PrP 106 ± 126 (Forloni et al, 1993;Perovic et al, 1995) is not yet fully understood. PrP C is present predominantly in the brain, where it may play a role in synaptic function (Collinge et al, 1994), but lower amounts of this protein have also been detected in other tissues (Bendheim et al, 1992).…”

“…At present, only a few drugs are known which may protect animals against PrP Sc infection and suppress PrP Sc -induced neurotoxicity: (i) polyanio-nic glycans, including pentosan sulfate and dextran sulfate, have been shown to prolong the incubation period and to inhibit PrP Sc formation in rodents (Diringer and Ehlers, 1991), most likely by reducing of the amount of PrP C on the cell surface through enhanced endocytosis of PrP C (Shyng et al, 1995); (ii) the polyene macrolide antibiotic, amphotericin B (Pocchiari et al, 1989), and its derivative, MS-8209 (Adjou et al, 1995), also cause a prolongation of the incubation period of PrP Sc -infected mice; (iii) the accumulation of PrP Sc could also be blocked by Congo red (Caughey and Race, 1992) and (iv) the anthracycline 4'-iodo-4'-deoxy-doxorubicin, which bind to amyloid ®brils (Tagliavini et al, 1997); (v) the neutotoxic effect displayed by PrP Sc was found to be prevented by antagonists of NMDA receptor channels, such as memantine and MK-801 Perovic et al, 1995;Brown et al, 1996); and (vi) the triaminopyridine¯upirtine, a clinically used non-opiod analgesic drug, was found to display in vitro a strong cytoprotective effect on neurons treated with PrP Sc or its toxic fragment, PrP 106 ± 126 (Perovic et al, 1994. This drug enhances the level of the antiapoptotic protein Bcl-2 and normalizes the level of intracellular glutathione (Perovic et al, 1996.…”