Abstract
The discovery of disease modifying anti-Alzheimer’s molecules continues to be dared by: disease target multiplicity, downstream neurodegenerative biochemistry complexities, and genotype implications. A confluence of the above ingredients has contributed to a pipeline of creative molecules that regrettably underperform in clinical trials. Thus far, only five palliative pharmacotherapeutic agents, that is, four acetylcholine potentiating agents and an N-methyl-D-aspartate (NMDA) antagonist are clinically available. In this review we collectively describe the currently suggested targetable pathways for designing anti-Alzheimer’s agents (palliative and/or disease modifying). We are prompted to contribute in this manner out of a desire to simplify and consolidate, to a certain extent, the divergent target literature on Alzheimer’s drug discovery. We herein provide a summary update and perspective on realized and potentially druggable pharmacological targets for this CNS disorder. This article covers mostly the 2005-2015 medicinal chemistry/pharmacological/biological literature space on the subject.
Keywords: ApoE, α-/β-/γ-/δ-Secretases, epigenetics, incretins, liver-x-receptors, presinilins, Tau, Wnt.
Mini-Reviews in Medicinal Chemistry
Title:Alzheimer’s Drug Discovery Maze: A Snap View of the Past Decade’s Diverse Pharmacological Targets for the Disorder
Volume: 17 Issue: 3
Author(s): Donald Sikazwe, Raghunandan Yendapally, Sushma Ramsinghani and Malik Khan
Affiliation:
Keywords: ApoE, α-/β-/γ-/δ-Secretases, epigenetics, incretins, liver-x-receptors, presinilins, Tau, Wnt.
Abstract: The discovery of disease modifying anti-Alzheimer’s molecules continues to be dared by: disease target multiplicity, downstream neurodegenerative biochemistry complexities, and genotype implications. A confluence of the above ingredients has contributed to a pipeline of creative molecules that regrettably underperform in clinical trials. Thus far, only five palliative pharmacotherapeutic agents, that is, four acetylcholine potentiating agents and an N-methyl-D-aspartate (NMDA) antagonist are clinically available. In this review we collectively describe the currently suggested targetable pathways for designing anti-Alzheimer’s agents (palliative and/or disease modifying). We are prompted to contribute in this manner out of a desire to simplify and consolidate, to a certain extent, the divergent target literature on Alzheimer’s drug discovery. We herein provide a summary update and perspective on realized and potentially druggable pharmacological targets for this CNS disorder. This article covers mostly the 2005-2015 medicinal chemistry/pharmacological/biological literature space on the subject.
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Sikazwe Donald, Yendapally Raghunandan, Ramsinghani Sushma and Khan Malik, Alzheimer’s Drug Discovery Maze: A Snap View of the Past Decade’s Diverse Pharmacological Targets for the Disorder, Mini-Reviews in Medicinal Chemistry 2017; 17 (3) . https://dx.doi.org/10.2174/1389557516666160822152625
DOI https://dx.doi.org/10.2174/1389557516666160822152625 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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