Effects of fructose-1,6-bisphosphate on morphological and functional neuronal integrity in rat hippocampal slices during energy deprivation

Fructose-1,6-bisphosphate attenuates induction of nitric oxide synthase in microglia stimulated with lipopolysaccharide

“…On the basis of these results, it has been suggested that mechanisms other than augmented carbohydrate metabolism are responsible for previous reports of neuronal protection by FBP (Hofer et al, 2009). Indeed, the protective role of FBP has been attributed to a variety of mechanisms such as the reduction of glutamate (Bickler and Buck, 1996), the mitigation of oxidative stress (Park et al, 2004;Vexler et al, 2003), calcium chelation (Bickler and Kelleher, 1992) and antagonism of NMDA receptors (Izumi et al, 2003). In addition, FBP initiates a series of neuroprotective signals, including phospholipase C (PLC) activation and increased activity of the MEK/ERK signaling pathway (Fahlman et al, 2002;Song et al, 2005) and up-regulates the expression of APE/Ref-1, an enzyme responsible for the repair of DNA (Long et al, 2002).…”

“…Fructose-1,6-bisphosphate (FBP) is a glycolytic intermediate which has a neuroprotective effect in various brain injury models (Izumi et al, 2003;Kaakinen et al, 2006;Park et al, 2004;Stringer and Xu, 2008;Vexler et al, 2003). The neuroprotection by FBP has been attributed to the maintenance of ATP levels (Cardenas et al, 2000;Espanol et al, 1998) and the reduction of glutamate (Bickler and Buck, 1996) and oxidative stress (Park et al, 2004;Vexler et al, 2003).…”

“…The neuroprotection by FBP has been attributed to the maintenance of ATP levels (Cardenas et al, 2000;Espanol et al, 1998) and the reduction of glutamate (Bickler and Buck, 1996) and oxidative stress (Park et al, 2004;Vexler et al, 2003). Other possible mechanisms have also been suggested, including calcium chelation (Bickler and Kelleher, 1992), antagonism of NMDA receptors (Izumi et al, 2003) and modulation of second messenger systems (Donohoe et al, 2001;Fahlman et al, 2002;Song et al, 2005). However, mechanisms whereby FBP protects the brain have not been fully elucidated yet.…”

Neuroprotection by fructose-1,6-bisphosphate involves ROS alterations via p38 MAPK/ERK

“…However, Izumi et al [18] suggested the neuroprotective effect of FBP were mediated by mechanism other than anaerobic energy supply. In an NMDA insult model, Ca 2+ influx through NMDA channels induced an increase of ROS and a subsequent excitotoxic neuronal death.…”

Fructose-1,6-bisphosphate suppresses lipopolysaccharide-induced expression of ICAM-1 through modulation of toll-like receptor-4 signaling in brain endothelial cells

“…In this context, alternative mechanisms other than augmentation of energy metabolism have been suggested for the neuroprotective action of FBP. Those include the attenuation of oxidative stress [15,29,51,52], the antagonism of NMDA receptors [53], calcium chelation [54], the enhancement of DNA repairing ability [55] and the regulation of signaling molecules such as phospholipase C and MEK/ERK [50,52,56]. Modulation of TLR4 signaling shown in the present study could be added to the above list.…”