From single target to multitarget/network therapeutics in Alzheimer's therapy

Brain network dysfunction in Alzheimer's disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2014-01, Vol.7 (2), p.113-135
Main Authors: Zheng, Hailin, Fridkin, Mati, Youdim, Moussa
Format: Article
Language:English
Subjects:
AChE-MAO-A/B inhibitor
Alzheimer's disease
chelator
Enzymes
Ginkgo biloba
Ligands
M30
M30D
memantine
nitromemantine
NMDA antagonist
Pharmacology
Review
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Summary:Brain network dysfunction in Alzheimer's disease (AD) involves many proteins (enzymes), processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although this paradigm has achieved considerable success in some particular diseases, it has failed to provide effective approaches to AD therapy. Network medicines may offer alternative hope for effective treatment of AD and other complex diseases. In contrast to the single-target drug approach, network medicines employ a holistic approach to restore network dysfunction by simultaneously targeting key components in disease networks. In this paper, we explore several drugs either in the clinic or under development for AD therapy in term of their design strategies, diverse mechanisms of action and disease-modifying potential. These drugs act as multi-target ligands and may serve as leads for further development as network medicines.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph7020113