In clinical and experimental settings, a great deal of effort is being made to protect
cells and tissues against harmful conditions and to facilitate metabolic recovery following
these insults. Much of the recent attention has focused on the protective role of a natural form
of sugar, fructose 1,6-bisphosphate (F16bP).
F16bP is a high-energy glycolytic intermediate that has been shown to exert a protective action
in different cell types and tissues (including the brain, kidney, intestine, liver and heart)
against various harmful conditions. For example, there is much evidence that it prevents neuronal
damage due to hypoxia and ischemia. Furthermore, the cytoprotective effects of F16bP
have been documented in lesions caused by chemicals or cold storage, in a decrease in mortality
during sepsis shock and even in the prevention of bone loss in experimental osteoporosis.
Intriguingly, protection in such a variety of targets and animal models suggests that the
mechanisms induced by F16bP are complex and involve different pathways.
In this review we will discuss the most recent theories concerning the molecular model of action
of F16bP inside cells. These include its incorporation as an energy substrate, the mechanism
for the improvement of ATP availability, and for preservation of organelle membrane
stability and functionality. In addition we will present new evidences regarding the capacity
of F16bP to decrease oxidative stress by limiting free radical production and improving antioxidant
systems, including the role of nitric oxide in the protective mechanism induced by
F16bP. Finally we will review the proposed mechanisms for explaining its anti-inflammatory,
immunomodulatory and neuroprotective properties.