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Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:285-301. doi: 10.1016/j.neubiorev.2014.06.007. Epub 2014 Jun 24.

Aberrant Rho GTPases signaling and cognitive dysfunction: in vivo evidence for a compelling molecular relationship.

Author information

1
Sect. Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Roma, Italy. Electronic address: bianca.defilippis@iss.it.
2
Sect. Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Roma, Italy; Bambino Gesù, Children Hospital, IRCCS, Roma, Italy.
3
Sect. Behavioural Neuroscience, Department of Cell Biology & Neuroscience, Istituto Superiore di Sanità, Roma, Italy.

Abstract

Rho GTPases are key intracellular signaling molecules that coordinate dynamic changes in the actin cytoskeleton, thereby stimulating a variety of processes, including morphogenesis, migration, neuronal development, cell division and adhesion. Deviations from normal Rho GTPases activation state have been proposed to disrupt cognition and synaptic plasticity. This review focuses on the functional consequences of genetic ablation of upstream and downstream Rho GTPases molecules on cognitive function and neuronal morphology and connectivity. Available information on this issue is described and compared to that gained from mice carrying mutations in the most studied Rho GTPases and from pharmacological in vivo studies in which brain Rho GTPases signaling was modulated. Results from reviewed literature provide definitive evidence of a compelling link between Rho GTPases signaling and cognitive function, thus supporting the notion that Rho GTPases and their downstream effectors may represent important therapeutic targets for disorders associated with cognitive dysfunction.

KEYWORDS:

Actin cytoskeleton; Cognitive dysfunction; Mouse models; Neural morphology; Rho GTPases; Structural plasticity

PMID:
24971827
DOI:
10.1016/j.neubiorev.2014.06.007
[Indexed for MEDLINE]

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