Bolognin Silvia, Lorenzetto Erika, Diana Giovanni, Buffelli Mario
Department of Neurological and Movement Sciences, Section of Physiology, University of Verona, Strada le Grazie 8, 37134, Verona, Italy,
Mol Neurobiol. 2014 Oct;50(2):406-22. doi: 10.1007/s12035-014-8637-5. Epub 2014 Jan 23.
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.
阿尔茨海默病（AD）的特征是广泛的突触和树突棘丧失。尽管付出了巨大努力，但驱动这种有害改变的分子机制尚未确定。在可能介导神经元连接丧失的因素中，Rho GTP酶的作用尤为令人关注。该蛋白家族传统上被认为是肌动蛋白细胞骨架重塑和树突棘维持的关键调节因子，但最近对其调节复杂动态的新见解表明，其信号级联在生理和病理条件下仍大多未知。在这里，我们综述了越来越多的证据，支持Rho GTP酶可能参与树突棘丧失，这是早期AD发病机制中一个公认的标志。我们还讨论了对Rho GTP酶信号框架的一些新见解，这些见解可能解释已发表的一些有争议的结果。对AD与Rho GTP酶之间联系的研究代表了一条颇具潜力的全新途径，具有治疗潜力。
