Department of Psychiatry & Behavioral Medicine, Institute for Research in Psychiatry Neuroimmunology Laboratory, University of South Florida College of Medicine, Tampa, FL 33613, USA.
CNS Neurol Disord Drug Targets. 2010 Apr;9(2):149-55. doi: 10.2174/187152710791012099.
As the number of elderly individuals rises, Alzheimer's disease (AD), marked by amyloid-beta deposition, neurofibrillary tangle formation, and low-level neuroinflammation, is expected to lead to an ever-worsening socioeconomic burden. AD pathoetiologic mechanisms are believed to involve chronic microglial activation. This phenomenon is associated with increased expression of membrane-bound CD40 with its cognate ligand, CD40 ligand (CD40L), as well as increased circulating levels of soluble forms of CD40 (sCD40) and CD40L (sCD40L). Here, we review the role of this inflammatory dyad in the pathogenesis of AD. In addition, we examine potential therapeutic strategies such as statins, flavonoids, and human umbilical cord blood transplantation, all of which have been shown to modulate CD40-CD40L interaction in mouse models of AD. Importantly, therapeutic approaches focusing on CD40-CD40L dyad regulation, either alone or in combination with amyloid-beta immunotherapy, may provide for a safe and effective AD prophylaxis or treatment in the near future.
随着老年人口的增加，阿尔茨海默病（AD）预计将导致日益严重的社会经济负担，其特征是淀粉样蛋白-β沉积、神经原纤维缠结形成和低水平的神经炎症。AD 的发病机制被认为涉及慢性小胶质细胞激活。这种现象与膜结合 CD40 及其同源配体 CD40 配体（CD40L）的表达增加以及可溶性 CD40（sCD40）和 CD40L（sCD40L）的循环水平升高有关。在这里，我们回顾了这一炎症对偶在 AD 发病机制中的作用。此外，我们还研究了一些潜在的治疗策略，如他汀类药物、类黄酮和人脐带血移植，所有这些都已被证明可以调节 AD 小鼠模型中的 CD40-CD40L 相互作用。重要的是，专注于 CD40-CD40L 对偶调节的治疗方法，无论是单独使用还是与淀粉样蛋白-β免疫疗法联合使用，都可能在不久的将来为 AD 的预防或治疗提供安全有效的方法。
