Combining in vitro and in silico Approaches to Find New Candidate Drugs Targeting the Pathological Proteins Related to the Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) as the most common cause of dementia among older people has aroused the universal concern of the whole world. However, until now there is still none effective treatments. Consequently, the development of new drugs targeting this complicated brain disorder is urgent and needs more efforts. In this review, we detailed the current state of knowledge about new candidate drugs targeting the pathological proteins especially the drugs which are employed using the combined methods of in vitro and in silico.

Methods: We looked up and reviewed online papers related to the pathogenesis and new drugs development of AD. Then, articles up to the requirements were respectively analyzed and summaried to provide the latest knowledge about the pathogenic effect and the new candidate drugs targeting Aβ and Tau proteins.

Results: New candidate drugs targeting the Aβ include decreasing the production, promoting the clearence and preventing aggregation. However these drugs have mostly failed in Phase III clinical trial stage due to the unsuccessful of reversing cognition symptoms. As to tau protein, the prevention of tau aggregation and propagation is a promising strategy to synthesize/design mechanismbased drugs against tauopathies. Some candidate drugs are under research. Moreover, because of the complex pathogenesis of AD, multi-target drugs have also shed light on the treatment of AD.

Conclusion: Given to the consecutive failure of Aβ-directed drugs and the feasibilities of tautargeted therapy, more and more researchers suggested that the AD treatment should be moved from Aβ to tau or focused on considering the soluble form of Aβ and tau as a whole. Moreover, the novel in silico methods also have great potential in drug discovery, drug repositioning, virtual screening of chemical libraries. No matter how many difficulties and challenges in prevention and treatment of AD, we firmly believe that the effective and safe drugs will be found using the combined methods in the immediate future with the global effort.

Keywords: AD new candidate drugs; Alzheimer's disease; amyloid β protein; in silico; in vitro; tau protein..