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Overexpression of
pro-inflammatory cytokines and cellular energy failure are associated
with neuroinflammatory disorders, such as Alzheimer’s disease.
Transgenic mice homozygous for human ApoE4 gene, a well known AD and
atherosclerosis animal model, show decreased levels of ATP, increased
inflammatory cytokines level and accumulation of beta amyloid in the
brain. All these findings are considered responsible for triggering
cognitive decline. We have demonstrated that a single administration of
the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside
inducing a strong amelioration of both spatial and emotional memory
deficits, favored the cell energy restore through an increment of ATP
content. This was accompanied by a modulation of cerebral Rho and Rac1
activity. Furthermore, CNF1 decreased the levels of beta amyloid
accumulation and interleukin-1b expression in the hippocampus.
Altogether, these data suggest that the pharmacological modulation of
Rho GTPases by CNF1 can improve memory performances in an animal model
of Alzheimer’s disease via acontrol of neuroinflammation and a rescue of systemic energy homeostasis.
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