We have previously reported that the Rho-activating Cytotoxic Necrotizing Factor 1 (CNF1) enhances cognitive performances, counteracts inflammatory pain, and triggers adult visual cortex functional plasticity in experimental animal models. CNF1 is a 113.8 Kda protein, produced by several Escherichia coli strains, which selectively and permanently activate the Rho GTPases, proteins primarily involved in the actin cytoskeleton regulation. In this work, we firstly demonstrate that CNF1 can specifically act on astrocytes, the most abundant type of glial cells in the central nervous system (CNS), which are involved in the induction of neuroinflammation. CNF1-treated astrocytes exert a supportive role for neurogenesis and reduce the production of the pro-inflammatory cytokine IL-1beta in vitro and also in vivo. In fact, in transgenic mice for ApoE4, a genetic risk factor for diseases with lipid metabolism and transport dysregulation and alteration of immune regulation (such as cerebral ischemia, brain infarction, arteriosclerosis, cerebral amyloid angiopathy, Alzheimer's disease etc.), CNF1 reduces hippocampal astrogliosis, brings ATP and IL-1beta to levels comparable to those of control ApoE3 animals, and decreases the beta amyloid accumulation. Reactive astrogliosis and inflammatory changes are also involved in all forms of seizures and, interestingly, CNF1 induces, even at sensorimotor cortex level, suppression of epileptiform phenomena in the DBA2/J mouse model of “petit mal” (Absence seizures). CNF1 can thus represent a unique pharmacological agent for treatment of those CNS disorders characterized by neuroinflammation and astrogliosis.

Use of CNF1 to treat neuroinflammation and astrogliosis in CNS diseases

CAMPANA, GABRIELE;RIMONDINI GIORGINI, ROBERTO;
2012

Abstract

We have previously reported that the Rho-activating Cytotoxic Necrotizing Factor 1 (CNF1) enhances cognitive performances, counteracts inflammatory pain, and triggers adult visual cortex functional plasticity in experimental animal models. CNF1 is a 113.8 Kda protein, produced by several Escherichia coli strains, which selectively and permanently activate the Rho GTPases, proteins primarily involved in the actin cytoskeleton regulation. In this work, we firstly demonstrate that CNF1 can specifically act on astrocytes, the most abundant type of glial cells in the central nervous system (CNS), which are involved in the induction of neuroinflammation. CNF1-treated astrocytes exert a supportive role for neurogenesis and reduce the production of the pro-inflammatory cytokine IL-1beta in vitro and also in vivo. In fact, in transgenic mice for ApoE4, a genetic risk factor for diseases with lipid metabolism and transport dysregulation and alteration of immune regulation (such as cerebral ischemia, brain infarction, arteriosclerosis, cerebral amyloid angiopathy, Alzheimer's disease etc.), CNF1 reduces hippocampal astrogliosis, brings ATP and IL-1beta to levels comparable to those of control ApoE3 animals, and decreases the beta amyloid accumulation. Reactive astrogliosis and inflammatory changes are also involved in all forms of seizures and, interestingly, CNF1 induces, even at sensorimotor cortex level, suppression of epileptiform phenomena in the DBA2/J mouse model of “petit mal” (Absence seizures). CNF1 can thus represent a unique pharmacological agent for treatment of those CNS disorders characterized by neuroinflammation and astrogliosis.
WO2013107910
Campana G.; Rimondini R.; Loizzo S.; Travglione S.; Malchiodi-Albedi F.; Fiorentini C.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/114323
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