CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova


Impact of the CD40-CD40L Dyad in Alzheimers Disease

Author(s): Brian Giunta, Kavon Rezai-Zadeh and Jun Tan

Affiliation: Department of Psychiatry&Behavioral Medicine, Institute for Research in Psychiatry Neuroimmunology Laboratory, University of South Florida, College of Medicine, MDC 102, Tampa, FL 33613, USA.


As the number of elderly individuals rises, Alzheimers disease (AD), marked by amyloid-β 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-β immunotherapy, may provide for a safe and effective AD prophylaxis or treatment in the near future.

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Article Details

Page: [149 - 155]
Pages: 7
DOI: 10.2174/187152710791012099