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:Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, 4301 Broadway, CPO: 99
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.