Send Orders for Reprints to reprints@benthamscience.ae Current Drug Metabolism, 2015, 16, 719-727 719  An Overview on Global Trends in Nanotechnological Approaches for Alzheimer Therapy Ghulam Md. Ashraf 1,* , Shams Tabrez 1 , Nasimudeen R. Jabir 1 , C.K. Firoz 1 , Saheem Ahmad 2 , Iftekhar Hassan 3 , Athanasios Alexiou 4 and Mohammad Amjad Kamal 1,5 1 King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia; 2 Department of Biosciences, Integral University, Lucknow, U.P., India; 3 Department of Zoology, College of Sciences, King Saud University, Riyadh, Saudi Arabia; 4 BiHELab, Department of Informatics, Ionian University, 49100 Corfu, Greece; 5 Enzymoic, Peterlee Pl, Hebersham, NSW 2770, Australia Abstract: Despite extensive research for over two decades, the medical science is yet to assign the exact aetiology and mode of progression of Alzheimer's disease (AD). The modern era of AD drug development began with the proposal of the cholinergic hypothesis of memory impairment. Since then, despite the proposal and phase trials of many therapeutic options, only few drugs have shown some efficacy and safety. The reasons behind this have been many including the ineffectiveness of tested drugs and inadequacy of clinical development methods. In this manu- script, we present an account of modern structural, functional and molecular imaging developed for AD therapy. A comprehensive re- view of all the current and future treatment options for AD, ranging from cholinergic drugs, NMDA receptor antagonist, immunotherapy, drugs reducing A production, and drugs targeting tau protein and mitochondrial dysfunction has also been provided. However, the fail- ure of all the proposed treatment options to provide a complete cure of AD has been pushing for the need of new therapies. The recent advent of nano-drugs has been proposed to provide crucial breakthroughs in AD therapy. Hence, a detailed outline of the usage and ap- plications of nano-drugs in AD therapy, and outstanding developments in nanodrug metabolism and disposition has been discussed. Keywords: AD imaging, Alzheimer's disease, nano-drugs, nanotechnology, therapy. 1. INTRODUCTION Alzheimer’s disease (AD) is the most common neurological disorder faced mainly by elderly individuals, and is characterized with progressive loss of neuronal and intellectual abilities [1, 2]. With better health care facilities preventing unnatural deaths, the ageing population is at greater susceptibility worldwide that might make AD a future epidemic posing a prominent medical challenge with social and economic burden [3, 4]. Despite extensive research to find out an effective treatment/therapy of AD, no substantial advancement has been made so far. The current mode of AD ther- apy is mainly restricted around its symptomatic treatment and that too doesn’t last long or the symptoms revert after some time. In spite of accelerated clinical and experimental studies based investi- gations in the recent times, it seems difficult to get an effective breakthrough very soon because of not so encouraging results available from randomised controlled trials (RCTs) [5]. The not so encouraging results of RCTs have been attributed to faults in the choice of drug(s) as well as programmes, thus proclaiming the need to amend the “one protein-one drug-one disease” hypothesis for AD therapy [6, 7]. Another major hurdle in the development of AD therapy has been the continuous attempt to design and synthesize novel compounds free form side effects, which further delays *Address correspondence to this author at the King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; Tel/Fax: +966593594931; E-mails: ashraf.gm@gmail.com, gashraf@kau.edu.sa clinical trials [5]. However, enhanced research focused on biologi- cal aspects, mechanistic therapeutic targets and pharmacodynamics is expected to improve drug safety and efficacy. Recent advancements in AD research have shifted the pathoge- netic focus to genes and proteins, promoting a target driven results in the arena of drug development [8]. However, AD pathogenesis pathway involving gene and proteins is non-linear and unpredict- able because of varied interactions occurring at different sub- cellular levels [9]. Infact, a network model of protein-drug interac- tions is expected to be more suitable than linear protein-drug model, because drugs mostly bind to more than one target [10]. The most conventional strategy of designing multi-target AD therapy in- volves the prescription of acetylcholinesterase (AChE) inhibitors along with N-methyl-D-aspartate (NMDA) receptor agonists [11]. Development of drugs possessing two or more active ingredients delivered in a single dose can be another strategy for developing multi-target AD therapy [12]. However, both these strategies are obstructed by the regulation of constituent drug or ingredient whose safety and efficiency have to be balanced at individual as well as in combination level [5]. One more strategy for multi-target AD ther- apy involves designing of drug(s) with selective polyphramacology, which are now in preclinical stage [9, 10]. Above discussed find- ings suggest that a single therapy for AD is not sufficient to contain the disease and this changed paradigm has become the focus of research based on the target proteins and organelles, besides multi- target-directed ligands approach. In addition, more promising RCTs developed with collaboration between basic and clinical Ghulam Md Ashraf 1875-5453/15 $58.00+.00 © 2015 Bentham Science Publishers Personal Use Only Not For Distribution