Therapeutic effects of the Rho GTPase modulator CNF1 in a model of Parkinson's disease.

Recent evidence suggests an early involvement of dopaminergic (DA) processes and terminals in Parkinson's disease (PD). The arborization of neurons depends on the actin cytoskeleton, which in turn is regulated by small GTPases of the Rho family, encompassing Rho, Rac and Cdc42 subfamilies. Indeed, some reports point to a role for Rac and Cdc42 signaling in the pathophysiology of inherited parkinsonisms.

Rho GTPase-dependent plasticity of dendritic spines in the adult brain.

Brain activity is associated with structural changes in the neural connections. However, in vivo imaging of the outer cortical layers has shown that dendritic spines, on which most excitatory synapses insist, are predominantly stable in adulthood. Changes in dendritic spines are governed by small GTPases of the Rho family through modulation of the actin cytoskeleton.

Long-lasting efficacy of the cognitive enhancer cytotoxic necrotizing factor 1.

Rho GTPases are key regulators of the activity-dependent changes of neural circuits. Besides being involved in nervous system development and repair, this neural structural plasticity is believed to constitute the cellular basis of learning and memory. Here we report that concurrent modulation of cerebral Rho GTPases, including Rac, Rho and Cdc42 subfamilies, by Cytotoxic Necrotizing Factor 1 (CNF1, 10 fmol/kg intracerebroventricularly) improves object recognition in both C57BL/6J and CD1 mice.

The Rho GTPase activating CNF1 improves associative working memory for object-in-place.

Cerebral Rho GTPases are crucially involved in cognitive abilities. This activity is thought to be related to the regulation of actin polymerization and, thereby, of the shape of the dendritic tree. Here we report that Cytotoxic Necrotizing Factor 1 (CNF1, 1fmol/kgicv), a bacterial protein endowed with Rho GTPase activating properties, enhances working memory for object location/discrimination in C57BL/6 mice.