Drug Design and Discovery in Alzheimer’s Disease

Republished Version of Frontiers in Drug Design and Discovery Volume 6

by

Atta-ur-Rahman, Mohammad Iqbal Choudhary

DOI: 10.2174/97816080582281150101
eISBN: 978-1-60805-822-8, 2014
ISBN: 978-1-60805-823-5
ISSN: 1574-0889 (Print)
ISSN: 2212-1064 (Online)



Recommend this eBook to your Library

Indexed in: Scopus, EMBASE

“Frontiers in Drug Design and Discovery” is an Ebook series devoted to publishing the latest and the most important advances in drug d...[view complete introduction]

Table of Contents

Preface

- Pp. i-iii (3)

Atta-ur-Rahman and M. Iqbal Choudhary

Download Free

List of Contributors

- Pp. iv-xi (8)

Atta-ur-Rahman and M. Iqbal Choudhary

Download Free

Pharmacotherapy of Alzheimer's Disease: Current State and Future Perspectives

- Pp. 3-39 (37)

Jan Korabecny, Filip Zemek, Ondrej Soukup, Katarina Spilovska, Kamil Musilek, Daniel Jun, Eugenie Nepovimova and Kamil Kuca

View Abstract Purchase Chapter

Challenges in Designing Therapeutic Agents for Treating Alzheimer’s Disease-from Serendipity to Rationality

- Pp. 40-141 (102)

Umer Rashid and Farzana L. Ansari

View Abstract Purchase Chapter

Enzyme Inhibitors Involved in the Treatment of Alzheimer’s Disease

- Pp. 142-198 (57)

Vageesh Revadigar, Raza Murad Ghalib, Vikneswaran Murugaiyah, Mohamed A. Embaby, Ali Jawad, Sayed Hasan Mehdi, Rokiah Hashim and Othman Sulaiman

View Abstract Purchase Chapter

Towards Small Molecules as Therapies for Alzheimer’s Disease and Other Neurodegenerative Disorders

- Pp. 199-290 (92)

Omar Aziz, Roland W. Bürli, David F. Fischer, Julie Frearson and Michael D. Wall

View Abstract Purchase Chapter

Multifunctional Enzyme Inhibition for Neuroprotection - A Focus on MAO, NOS, and AChE Inhibitors

- Pp. 291-365 (75)

Jacques Joubert, Jacobus P. Petzer, Louis H.A. Prins, Benjamin P. Repsold and Sarel F. Malan

View Abstract Purchase Chapter

Specific Cholinesterase Inhibitors: A Potential Tool to Assist in Management of Alzheimer Disease

- Pp. 366-386 (21)

Nigel H. Grieg, Mohammad A. Kamal, Nasimudeen R. Jabir, Shams Tabrez, Faizul H. Nasim, Adel M. Abuzenadah and Gjumrakch Aliev

View Abstract Purchase Chapter

Role of Acetylcholinesterase Inhibitors and Alzheimer Disease

- Pp. 387-425 (39)

Zafar Saied Saify and Nighat Sultana

View Abstract Purchase Chapter

Research Strategies Developed for the Treatment of Alzheimer’s Disease. Reversible and Pseudo-Irreversible Inhibitors of Acetylcholinesterase: Structure-Activity Relationships and Drug Design

- Pp. 426-477 (52)

Mauricio Alcolea-Palafox, Paloma Posada-Moreno, Ismael Ortuño- Soriano, José L. Pacheco-del-Cerro, Carmen Martínez-Rincón, Dolores Rodríguez-Martínez and Lara Pacheco-Cuevas

View Abstract Purchase Chapter

Modulation of BACE1 Activity as a Potential Therapeutic Strategy for Treating Alzheimer’s Disease

- Pp. 478-517 (40)



View Abstract Purchase Chapter

BACE1 Inhibitors: Attractive Therapeutics for Alzheimer’s Disease

- Pp. 518-546 (29)

Boris Decourt, MiMi Macias, Marwan Sabbagh and Abdu Adem

View Abstract Purchase Chapter

Combining BACE1 Inhibition with Metal Chelation as Possible Therapy for Alzheimer’s Disease

- Pp. 547-565 (19)

Maged M. Henary, Tyler L. Dost, Eric A. Owens and Surendra Reddy Punganuru

View Abstract Purchase Chapter

Somatostatin Receptor-4 Agonists as Candidates for Treatment of Alzheimer’s Disease

- Pp. 566-597 (32)

Karin E. Sandoval, Kenneth A. Witt, A. Michael Crider and Maria Kontoyianni

View Abstract Purchase Chapter

Neprilysin Inhibitors Provide Insight into its Specificity and Therapeutic Potential

- Pp. 598-622 (25)

Darrick Pope and Michael Cascio

View Abstract Purchase Chapter

Targeting the GSK3β/β-catenin Signaling to Treat Alzheimer´s Disease: Plausible or Utopic?

- Pp. 623-642 (20)

Fares Zeidán-Chuliá and José Cláudio Fonseca Moreira

View Abstract Purchase Chapter

Targets and Small Molecules Against Tauopathies. Part 1: From Genes to Soluble, Aggregation-Prone Tau Proteins

- Pp. 643-715 (73)

Pierfausto Seneci

View Abstract Purchase Chapter

Nanomedicine Based Drug Targeting in Alzheimer’s Disease: High Impact of Small Carter

- Pp. 716-739 (24)

Mohammad Zaki Ahmad, Sohail Akhter, Ziyaur Rahman, Javed Ahmad, Iqbal Ahmad and Farhan Jalees Ahmad

View Abstract Purchase Chapter

Index

- Pp. 740-766 (27)

Atta-ur-Rahman and M. Iqbal Choudhary

Download Free

Preface

Alzheimer’s disease (AD) is one of the most common neurological disorders, affecting a large portion of the human population in both the developed and the developing world. The demographic changes in the next few decades are likely to increase the prevalence of AD to epidemic proportions. Unfortunately, despite major advances in molecular and structural biology, neurochemistry, disease genomics and cell physiology, the etiology of the disease is only marginally understood. AD has been the focus of major research efforts, both in the pharmaceutical industry and in academia. The literature is continuously enriched by exciting discoveries on various aspects of AD and its prevention and treatment. It is nearly impossible for any researcher to remain on top of the most recent developments in this dynamic field without access to comprehensive reviews on various aspects.

This volume of the book series “Frontiers in Drug Discovery and Development” is focused on key developments in the understanding of the disease at molecular levels, identification and validation of molecular targets, as well as innovative approaches towards drug discovery, development and delivery. The volume comprises 16 scholarly written review articles by leading researchers in the field, covering a broad range of topics.

The review contributed by Korabecny et al sets the stage for the subsequent chapters by detailing the main symptomatic strategies available for the treatment of AD and for the improvement of quality of life of AD patients. This review summarizes various classes of current and future therapies of AD. Rashid and Ansari focus on the major challenges faced in the discovery and development of anti-AD drugs. They provide examples of several blockbuster AD drugs, obtained through various approaches. Revadigar and his team have contributed a chapter reviewing the literature about the identification of various enzymes involved in the on-set and progression of Alzheimer’s diseases. They have included numerous examples of inhibitors of these enzymes which has either already developed as drugs or are in various stages of drug development.

Aziz et al focus on the significance of small molecules, both natural and synthetic, as possible drug candidates for the treatment of neurodegenerative diseases, including AD.

The four review articles (chapters 5-8), contributed by Joubert et al, Grieg et al, Saify and Sultana, and Alcolea-Palafox et al, specifically focus on the role of cholinesterases in the on-set and progression of AD and their inhibition, which has potential as an effective treatment. It is important to note that most of the current therapies of AD are based on cholinesterase modulation and the field remains active.

Beta-site APP clearing enzyme-1 (BACE-1) plays an important role in the production of β-amyloid proteins, one of the key reasons of the progression of AD. BACE-1 has been identified as the key target for the development of anti-AD therapies. Klaver and Tesco, Decourt et al, and Henary et al have contributed three excellent reviews (chapter 9-11) on the modulation of BACE-1 activity, as a strategy towards new drug discovery and development. Along with the small molecular inhibitors of BACE-1, the role of metal chelating agents has also been reviewed.

Along with two key targets, cholinesterase and BACl-1, a number of other targets have also been identified for drug discovery. Sandoval et al contributed a comprehensive review on various chemical compounds which serve as agonist of somatostatin subtype-4 receptor as a possible treatment regimen for AD. Neprilysin, a key target in the etiology of AD, has been the focus of recent research. Neprilysin catalyzes the degradation of amyloid beta peptides (Aβ), which are neurotoxins and contribute in the pathophysiology of AD. Pope and Cascio have reviewed the recent work on the inhibition of neprilysin and the prospects of their development as treatment for AD.

GSK3β/β-catenin signaling has been identified as a possible contributor to the onset and progressive degeneration of neuron in AD. GSK-3 controls proteosomal degradation of catenin, thus slowdown, the neurodegeneration. Zeidán-Chuliá and Moreira have critically analyzed its validity as a target for anti-AD drug discovery.

Seneci covers the important aspects of AD treatment and inhibition of phosphorylation of tau-proteins, collectively called taupathy. The focus has been to understand the expression of such proteins at the genetic level and to identify the structural characteristics which makes them aggregatory in nature. Another aim is to use small molecules as effective inhibitors of these processes. Last but not least, the article contributed by Ahmed et al comprehensively reviews the applications of nanotechnology in the development of effective drug delivery vehicles for AD drugs. Nanomedicines can serve as novel carrier of cholinesterase inhibitors effectively crossing the anatomical and biochemical barriers. We wish to express our profound thanks to all the contributors of reviews in this volume for their hard, and scholarly work and critical commentary. We are confident that their scholarly contributions will make this volume of great interest to many researches. We are also grateful to Mr. Mahmood Alam (Director Publication) and Ms. Sara Yaser (Manager Publications) of Bentham Science Publishers for their excellent management skills and secretarial support.

Atta-ur-Rahman, FRS
Honorary Life Fellow, Kings College
University of Cambridge
UK

M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Pakistan

List of Contributors

Editor(s):
Atta-ur-Rahman
University of Cambridge
Cambridge
UK


Mohammad Iqbal Choudhary
H.E.J. Research Institute of Chemistry
International Center for Chemical and Biological Sciences
University of Karachi
Karachi
Pakistan




Contributor(s):
A. Michael Crider
Faculty of Medicine and Health Sciences
United Arab Emirates University
Department Pharmacology and Therapeutics
Al Ain
UAE


Abdu Adem
Faculty of Medicine and Health Sciences
United Arab Emirates University
Department Pharmacology and Therapeutics
Al Ain
UAE


Adel M. Abuzenadah
King Fahd Medical Research Center
King Abdulaziz University
P. O. Box 80216
Jeddah, 21589
Saudi Arabia


Ali Jawad
Department of Applied Physics
Zakir Husain College of Engineering and Technology
Aligarh Muslim University
Aligarh UP
India


Benjamin P. Repsold
Pharmaceutical Chemistry
North-West University
Private Bag X6001
Potchefstroom, 2520
South Africa


Boris Decourt
Banner Sun Health Research Institute
Sun City
AZ
USA


Carmen Martínez-Rincón
Nursing Department
Complutense University of Madrid
Spain


Daniel Jun
University Hospital Hradec Kralove
Sokolska 581
500 05 Hradec Kralove
Czech Republic


Darrick Pope
Department of Chemistry and Biochemistry
Duquesne University
Pittsburgh
PA, 15282
USA


David F. Fischer
BioFocus
Leiden
The Netherlands


David William Klaver
Department of Neuroscience
Alzheimer’s Disease Research Laboratory
Tufts University School of Medicine
Boston
MA
USA


Dolores Rodríguez-Martínez
Nursing Department
Complutense University of Madrid
Spain


Eric A. Owens
Department of Chemistry
Center for Diagnostics and Therapeutics
Georgia State University
Georgia
Atlanta, 30303
USA


Eugenie Nepovimova
Department of Toxicology
Faculty of Military Health Sciences
Trebesska 1575, 500 01
Hradec Kralove
Czech Republic


Faizul H. Nasim
Department of Chemistry, BJ Campus
The Islamia University of Bahawalpur
Bahawalpur
Pakistan


Fares Zeidán-Chuliá
Center of Oxidative Stress Research
Department of Biochemistry
Postgraduate Program in Biological Sciences
Biochemistry
Institute of Basic Health Sciences
Federal University of Rio Grande do Sul
Porto Alegre
RS
Brazil


Farhan Jalees Ahmad
Nanomedicine Research Lab
Department of Pharmaceutics
Faculty of Pharmacy
Jamia Hamdard
New Delhi 110062
India


Farzana L. Ansari
Department of Chemistry
Quaid-i-Azam University
Islamabad 45320
Pakistan


Filip Zemek
Department of Toxicology
Faculty of Military Health Sciences
Trebesska 1575
500 01 Hradec Kralove
Islamabad 45320
Czech Republic


Giuseppina Tesco
Alzheimer’s Disease Research Laboratory
Department of Neuroscience
Tufts University School of Medicine
500 01 Hradec Kralove
Boston
MA
USA


Gjumrakch Aliev
Department of Health Science and Healthcare Administration
University of Atlanta
Atlanta
GA
USA
/
GALLY International Biomedical Research Consulting LLC
University of Atlanta
San Antonio
TX
USA


Iqbal Ahmad
Nanomedicine Research Lab, Department of Pharmaceutics
Faculty of Pharmacy
Jamia Hamdard
New Delhi, 110062
India


Ismael Ortuño- Soriano
Institute for Health Research at the San Carlos Clinical Hospital (IdISSC)
Madrid
Spain
/
Nursing Department
Complutense University of Madrid
Madrid
Spain


Jacobus P. Petzer
Pharmaceutical Chemistry
North-West University
Private Bag X6001
Potchefstroom
South Africa


Jacques Joubert
School of Pharmacy
University of the Western Cape
Private Bag X17
Bellville, 7535
South Africa


Jan Korabecny
Department of Toxicology
Faculty of Military Health Sciences
Trebesska 1575
500 01 Hradec Kralove
Czech Republic


Javed Ahmad
Nanomedicine Research Lab
Department of Pharmaceutics, Faculty of Pharmacy
Jamia Hamdard
New Delhi, 110062
India


José Cláudio Fonseca Moreira
Center of Oxidative Stress Research
Department of Biochemistry
Postgraduate Program in Biological Sciences: Biochemistry
Institute of Basic Health Sciences
Federal University of Rio Grande do Sul
Porto Alegre
RS
Brazil


José L. Pacheco-del-Cerro
Nursing Department
Complutense University of Madrid
Madrid
Spain


Julie Frearson
BioFocus; Chesterford Research Park
Saffron Walden
Essex, CB10 1XL
UK


Kamil Kuca
University Hospital Hradec Kralove
Sokolska 581
500 05 Hradec Kralove
Czech Republic


Kamil Musilek
University Hospital Hradec Kralove
Sokolska 581
500 05 Hradec Kralove
Czech Republic


Karin E. Sandoval
Department of Pharmaceutical Sciences
Southern Illinois University Edwardsville
Edwardsville
Illinois, 62026
USA


Katarina Spilovska
Department of Toxicology
Faculty of Military Health Sciences
Trebesska 1575
500 01 Hradec Kralove
Czech Republic


Kenneth Witt
Department of Pharmaceutical Sciences
Southern Illinois University Edwardsville
Edwardsville
Illinois, 62026
USA


Lara Pacheco-Cuevas
Nursing Department
Complutense University of Madrid
Spain


Louis H.A. Prins
Department of Pharmacy
University of Namibia
Windhoek
Namibia


Maged M. Henary
Department of Chemistry, Center for Diagnostics and Therapeutics
Center for Biotechnology and Drug Design, Georgia State University
Georgia
Atlanta, 30303
USA


Maria Kontoyianni
Department of Pharmaceutical Sciences
Southern Illinois University Edwardsville
Edwardsville
Illinois, 62026
USA


Marwan Sabbagh
Banner Sun Health Research Institute
Sun City
AZ
USA


Mauricio Alcolea-Palafox
Chemical-Physics Department
Chemistry Faculty
Complutense University of Madrid
Madrid
Spain


Michael Cascio
Department of Chemistry and Biochemistry
Duquesne University
Pittsburgh
PA, 15282
USA


Michael D. Wall
BioFocus; Chesterford Research Park
Saffron Walden
Essex, CB10 1XL
UK


MiMi Macias
Banner Sun Health Research Institute
Sun City
AZ
USA


Mohamed A. Embaby
Department of Chemistry
Faculty of Sciences & Arts Khulais
King Abdulaziz University
Jeddah
KSA


Mohammad A. Kamal
King Fahd Medical Research Center
King Abdulaziz University
P. O. Box 80216
Jeddah, 21589
Saudi Arabia


Mohamed Zaki Ahmad
Department of Pharmaceutics
College of Pharmacy
Najran University
Saudi Arabia


Nasimudeen R. Jabir
King Fahd Medical Research Center
King Abdulaziz University
P. O. Box 80216
Jeddah, 21589
Saudi Arabia


Nigel H. Grieg
Drug Design & Development Section
Laboratory of Neurosciences
Intramural Research Program
National Institute on Aging
National Institutes of Health
Baltimore
MD 21224
USA


Mohamed Nighat Sultana
Pharmaceutical Research Center
PCSIR Laboratories Complex
Shahrah-e-Dr. Salimuzzaman Siddiqui
Karachi, 75280
Pakistan


Omar Aziz
Pharmaceutical Research Center
BioFocus; Chesterford Research Park
Saffron Walden
Essex, CB10 1XL
UK


Ondrej Soukup
University Hospital Hradec Kralove
Sokolska 581
500 05 Hradec Kralove
Czech Republic


Othman Sulaiman
School of Industrial Technology
Universiti Sains Malaysia
Pulau Pinang
Minden–11800
Malaysia


Paloma Posada-Moreno
Institute for Health Research at the San Carlos Clinical Hospital (IdISSC)
Madrid
Spain
/
Nursing Department
Complutense University of Madrid
Madrid
Spain


Pierfausto Seneci
Department of Chemistry
University of Milan
Via Golgi 19
I-20133 Milan
Italy


Raza Murad Ghalib
Department of Chemistry
Faculty of Sciences & Arts Khulais
King Abdulaziz University
Jeddah
KSA


Rokiah Hashim
School of Industrial Technology
Universiti Sains Malaysia
Pulau Pinang
Minden–11800
Malaysia


Sarel F. Malan
School of Pharmacy
University of the Western Cape
Private Bag X17
Bellville, 7535
South Africa


Sayed Hasan Mehdi
Department of Chemistry
SPG College
Lucknow
UP
India


Shams Tabrez
King Fahd Medical Research Center
King Abdulaziz University
P. O. Box 80216
Jeddah, 21589
Saudi Arabia


Sohail Akhter
Nanomedicine Research Lab
Department of Pharmaceutics, Faculty of Pharmacy
Jamia Hamdard
New Delhi, 110062
India


Surendra Reddy Punganuru
Department of Chemistry
Georgia State University
Georgia
Atlanta, 30303
USA


Tyler L. Dost
Department of Chemistry
Georgia State University
Georgia
Atlanta, 30303
USA


Umer Rashid
Department of Chemistry
Hazara University
Mansehra, 21120
Pakistan


Vageesh Revadigar
Discipline of Pharmacology
School of Pharmaceutical Sciences
Universiti Sains Malaysia
Pulau Pinang
Minden–11800
Malaysia


Vikneswaran Murugaiyah
Discipline of Pharmacology, School of Pharmaceutical Sciences
Universiti Sains Malaysia
Minden–11800
Pulau Pinang
Malaysia


Zafar Saied Saify
International Center for Chemical Sciences
H. E. J. Research Institute of Chemistry
University of Karachi
Karachi, 75270
Pakistan


Ziyaur Rahman
Irma Lerma Rangel College of Pharmacy
Texas A&M Health Science Center
Kingsville
Texas
USA




Advertisement


Related Journals



Related Books



Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science