title: CNF1 increases brain energy level, counteracts neuroinflammatory markers and rescues cognitive deficits in a murine model of Alzheimer's disease.
abstract: 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-1β 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 a control of neuroinflammation and a rescue of systemic energy homeostasis.
authors.affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Loizzo
authors.forename: Roberto
authors.initials: R
authors.lastname: Rimondini
authors.forename: Sara
authors.initials: S
authors.lastname: Travaglione
authors.forename: Alessia
authors.initials: A
authors.lastname: Fabbri
authors.forename: Marco
authors.initials: M
authors.lastname: Guidotti
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferri
authors.forename: Gabriele
authors.initials: G
authors.lastname: Campana
authors.forename: Carla
authors.initials: C
authors.lastname: Fiorentini
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics; D001427:Bacterial Toxins / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001427:Bacterial Toxins; D015415:Biomarkers; D016207:Cytokines; D029968:Escherichia coli Proteins; C060296:cytotoxic necrotizing factor type 1; D000255:Adenosine Triphosphate; D020741:rho GTP-Binding Proteins