Pharmacophore-based models for therapeutic drugs against phosphorylated tau in Alzheimer's disease. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Pradeepkiran, Jangampalli Adi; Reddy, Arubala P.; Reddy, P. Hemachandra
• Is Part Of: Drug discovery today. Volume 24:Issue 2(2019)
• Page Start: 616
• Page End: 623
• Publication Date: 2019-02
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2018.11.005
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Tau plays an important part in the formation of axonal microtubules. Phosphorylated tau (P-tau) plays an aberrant part in causing Alzheimer's disease. P-tau is a potential therapeutic target in Alzheimer's disease and tauopathies. P-tau-targeted 3D pharmacophore drug models are important for Alzheimer's disease and tauopathies. Abstract : Phosphorylated tau (P-tau) has received much attention in the field of Alzheimer's disease (AD), as a potential therapeutic target owing to its involvement with synaptic damage and neuronal dysfunction. The continuous failure of amyloid β (Aβ)-targeted therapeutics highlights the urgency to consider alternative therapeutic strategies for AD. The present review describes the latest developments in tau biology and function. It also explains abnormal interactions between P-tau with Aβ and the mitochondrial fission protein Drp1, leading to excessive mitochondrial fragmentation and synaptic damage in AD neurons. This article also addresses 3D pharmacophore-based drug models designed to treat patients with AD and other tauopathies.