TY - JOUR
T1 - Combining in vitro and in silico approaches to find new candidate drugs targeting the pathological proteins related to the Alzheimer's disease
AU - Li, Hui
AU - Wang, Xiaobing
AU - Yu, Hongmei
AU - Zhu, Jing
AU - Jin, Hongtao
AU - Wang, Aiping
AU - Yang, Zhaogang
N1 - Publisher Copyright:
© 2018 Bentham Science Publishers.
PY - 2018
Y1 - 2018
N2 - 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 summa-ried 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 mechanism-based 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 tau-targeted 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.
AB - 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 summa-ried 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 mechanism-based 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 tau-targeted 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.
KW - AD new candidate drugs
KW - Alzheimer’s disease
KW - Amyloid β protein
KW - In silico
KW - In vitro
KW - Tau protein
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U2 - 10.2174/1570159X15666171030142108
DO - 10.2174/1570159X15666171030142108
M3 - Review article
C2 - 29086699
AN - SCOPUS:85048985957
SN - 1570-159X
VL - 16
SP - 758
EP - 768
JO - Current Neuropharmacology
JF - Current Neuropharmacology
IS - 6
ER -