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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Sep 9, 2015; 4(3): 236-264
Published online Sep 9, 2015. doi: 10.5497/wjp.v4.i3.236
Therapeutic targets and delivery challenges for Alzheimer’s disease
Preshita Desai, Harshad Shete, Rahul Adnaik, John Disouza, Vandana Patravale
Preshita Desai, Harshad Shete, Vandana Patravale, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India
Rahul Adnaik, Department of Pharmacology, Rajarambapu College of Pharmacy, Sangli 415404, Maharashtra, India
John Disouza, Tatyasaheb Kore College of Pharmacy, Kolhapur 416113, Maharashtra, India
Author contributions: Desai P and Shete H contributed equally to the paper; all the authors contributed to this paper.
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vandana Patravale, PhD, Professor of Pharmaceutics, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga (East), Mumbai 400019, Maharashtra, India. vbp_muict@yahoo.co.in
Telephone: +91-22-33612217 Fax: +91-22-33611020
Received: November 23, 2014
Peer-review started: November 23, 2014
First decision: December 12, 2014
Revised: May 29, 2015
Accepted: August 10, 2015
Article in press: August 11, 2015
Published online: September 9, 2015
Processing time: 289 Days and 12.6 Hours
Abstract

Dementia, including Alzheimer’s disease, the 21st Century epidemic, is one of the most significant social and health crises which has currently afflicted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-inflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately leading to Alzheimer’s disease cure.

Keywords: Neurofibrillary tangles; Alzheimer’s disease; Dementia; Amyloid β; Tau; Neurodegeneration; Blood brain barrier; Transdermal; Nasal

Core tip: Dementia, including Alzheimer’s disease, the 21st Century epidemic, is one of the most significant social and health crises which has currently afflicted nearly 44 million patients worldwide and is on rampant rise. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus focuses on thorough understanding of Alzheimer’s disease pathophysiology, pharmacotherapy in terms of explored therapeutic targets and drug delivery systems towards better delivery of anti-Alzheirmer actives and a possible way ahead.