title: Alzheimer's Drug Discovery Maze: A Snap View of the Past Decade's Diverse Pharmacological Targets for the Disorder.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, 4301 Broadway, CPO: 99,. United States.
authors.forename: Donald
authors.initials: D
authors.lastname: Sikazwe
authors.forename: Raghunandan
authors.initials: R
authors.lastname: Yendapally
authors.forename: Sushma
authors.initials: S
authors.lastname: Ramsinghani
authors.forename: Malik
authors.initials: M
authors.lastname: Khan
mesh_terms: D000109:Acetylcholine / Q000737:chemistry / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D002802:Cholinesterases; D000109:Acetylcholine