Current and novel therapeutic molecules and targets in Alzheimer's disease

• Main Authors: Ashwini Kumar, Chaluveelaveedu Murleedharan Nisha, Chitrangda Silakari, Isha Sharma, Kanukanti Anusha, Nityasha Gupta, Prateek Nair, Timir Tripathi, Awanish Kumar
• Format: Article
• Language: English
• Published: Elsevier 2016-01-01
• Series: Journal of the Formosan Medical Association
• Subjects: Alzheimer's disease; drug targets; inhibitors; molecular docking; therapy
• Online Access: http://www.sciencedirect.com/science/article/pii/S0929664615001497

Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline, i.e., dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine, etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for the selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD, and future prospects of the docking with particular emphasis on AD.