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The Potential Role of Rho GTPases in Alzheimer's Disease Pathogenesis

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Abstract

Alzheimer's disease (AD) is characterized by a wide loss of synapses and dendritic spines. Despite extensive efforts, the molecular mechanisms driving this detrimental alteration have not yet been determined. Among the factors potentially mediating this loss of neuronal connectivity, the contribution of Rho GTPases is of particular interest. This family of proteins is classically considered a key regulator of actin cytoskeleton remodeling and dendritic spine maintenance, but new insights into the complex dynamics of its regulation have recently determined how its signaling cascade is still largely unknown, both in physiological and pathological conditions. Here, we review the growing evidence supporting the potential involvement of Rho GTPases in spine loss, which is a unanimously recognized hallmark of early AD pathogenesis. We also discuss some new insights into Rho GTPase signaling framework that might explain several controversial results that have been published. The study of the connection between AD and Rho GTPases represents a quite unchartered avenue that holds therapeutic potential.

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Acknowledgments

This work was supported by funding of the University of Verona, “Fondazione Cariverona” project Verona Nanomedicine Initiative.

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Authors and Affiliations

  1. Department of Neurological and Movement Sciences, Section of Physiology, University of Verona, Strada le Grazie 8, 37134, Verona, Italy

    Silvia Bolognin, Erika Lorenzetto & Mario Buffelli

  2. Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy

    Giovanni Diana

  3. Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134, Verona, Italy

    Mario Buffelli

  4. National Institute of Neuroscience, Verona, Italy

    Mario Buffelli

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  1. Silvia Bolognin
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Correspondence to Silvia Bolognin.

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Bolognin, S., Lorenzetto, E., Diana, G. et al. The Potential Role of Rho GTPases in Alzheimer's Disease Pathogenesis. Mol Neurobiol 50, 406–422 (2014). https://doi.org/10.1007/s12035-014-8637-5

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