Molecular Neurobiology

, Volume 50, Issue 2, pp 406–422 | Cite as

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

  • Silvia BologninEmail author
  • Erika Lorenzetto
  • Giovanni Diana
  • Mario Buffelli


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.


Beta-amyloid Cytoskeleton Rho-GTPases 



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


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Silvia Bolognin
    • 1
    Email author
  • Erika Lorenzetto
    • 1
  • Giovanni Diana
    • 2
  • Mario Buffelli
    • 1
    • 3
    • 4
  1. 1.Department of Neurological and Movement Sciences, Section of PhysiologyUniversity of VeronaVeronaItaly
  2. 2.Department of Therapeutic Research and Medicines EvaluationIstituto Superiore di SanitaRomeItaly
  3. 3.Center for Biomedical ComputingUniversity of VeronaVeronaItaly
  4. 4.National Institute of NeuroscienceVeronaItaly

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