Frontiers in Clinical Drug Research – Alzheimer Disorders

Volume 1

by

Atta-ur-Rahman

DOI: 10.2174/97816080572211130101
eISBN: 978-1-60805-722-1, 2013
ISBN: 978-1-60805-723-8
ISSN: 2214-5168

  
  




Frontiers in Clinical Drug Research - Alzheimer Disorders is an e-Book series concerned with Alzheimer's disease (AD)...[view complete introduction]
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Table of Contents

Preface , Pp. i-ii (2)

Atta-ur-Rahman
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List of Contributors , Pp. iii-vi (4)

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Immunotherapy with Anti-Aβ Monoclonal Antibodies in Alzheimer’s Disease: A Critical Review on the Molecules in the Pipelines with Regulatory Considerations , Pp. 3-85 (83)

Chrystelle Mavoungou and Katharina Schindowski Zimmerman
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The Development of Multi-Target-Directed Ligands (MTDL) to Treat Alzheimer’s Disease , Pp. 86-108 (23)

John W. Wright and Joseph W. Harding
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Next Generation Drugs in Alzheimer's Disease Treatment: From Benchtop to Bedside , Pp. 109-146 (38)

Rosaria A. Cavallaro and Andrea Fuso
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Tau-Directed Therapies for Alzheimer’s Disease and Other Tauopathies , Pp. 147-182 (36)

Yasumasa Yoshiyama
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Different Approaches in the Treatment of Alzheimer's Disease: Comprehensive Insight , Pp. 183-216 (34)

Zaciragic Asija
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Alzheimer’s Disease and Dementia: A Midlife Approach to Treatment is Needed , Pp. 217-242 (26)

Angela Clifford, Jennifer Stock, Stephan Bandelow, Tri Budi Rahardjo and Eef Hogervorst
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Neurogenic Molecules Modulating Cell Survival Pathways, Amyloid Beta, Tau Proteins, and Metal Dyshomeostasis: An Alternative Hope for Alzheimer’s Therapy , Pp. 243-264 (22)

Hailin Zheng, Mati Fridkin and Moussa B.H. Youdim
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Cognitive Decline and Alzheimer's Disease: A Central Role for Hypoxia-Obstructive Sleep Apnea and Related Stigmata in Elderly , Pp. 265-314 (50)

Mak Adam Daulatzai
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Pharmacotherapies for Alzheimer’s Disease: From Natural Compounds to Target Synthetic Drugs , Pp. 315-366 (52)

Chuang Wang, Rui Wang, James M. O’Donnell and Ying Xu
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Challenges in the Morphological Diagnosis of Dementias , Pp. 367-410 (44)

Kurt A. Jellinger
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Metal Ions in the Pathogenesis of Alzheimer’s Disease: An Open Field , Pp. 411-431 (21)

Guido Crisponi, Valeria M. Nurchi, Daniela Fanni, Clara Gerosa, Sonia Nemolato, Miriam Crespo-Alonso, Leonardo Toso, Joanna I. Lachowicz and Gavino Faa
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Index , Pp. 432-456 (25)

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Preface

Alzheimer's disease (AD) is a disease that causes dementia, or loss of brain function. It affects the parts of the brain that deal with memory, thought, and language. The brain of a person with Alzheimer's contains abnormal clumps of cellular debris and protein (plaques) and collapsed microtubules (support structures of the cell).

The chapters in this volume are written by leading authors in their respective fields. There are several AD related topics in this introductory volume covering immunotherapy, AD diagnosis, symptomatic AD pathogenesis along with neurodegenerative effects, AD drug development models and therapy, and age related effects leading to AD.

In the first chapter of the eBook, Katharina Schindowski Zimmerman reviews the immunological basis for the mechanism of action of passive Aβ immunotherapy, anti-Aβ mAbs and scaffolds. In the next chapter, Wright and Harding review the approach of employing multi-target-directed ligands (MTDL) in the development of drugs to treat AD. The authors of this review demonstrate that there is a paradigm shift in drug screening, away from single lead-target models, and it could be potentially useful in treating AD. Chapter 3, written by Cavallaro and Fuso, summarizes current drugs used in AD therapy and new developments in therapeutic interventions in clinical phases. In the subsequent chapter Yohsiyama reviews the progress in tau-directed therapies. This work is significant from the standpoint of current clinical trials of therapies focusing on restricting beta –amyloid (Aβ) production in order to reduce Aβ pathogenesis and neurodegeneration in patients suffering from symptomatic AD. Asija provides a comprehensive insight into the different, currently available, approaches in the treatment of AD in chapter 5. The review presents findings of ongoing clinical trials and drug research studies in advanced stages of development and their application in the prevention and treatment of AD.

Physical activity and exercise is thought to play a positive role in improving the quality of life among patients suffering from brain disorders. Chapter 6 by Eef Hogervorst et al. takes on this perspective. The authors discuss factors that may influence the relationship between physical activity and cognitive functioning with the implications in theory theory and practice. Zheng et al. elaborate on some examples of neurogenic molecules which can reduce amyloid beta (Aβ) production, prevent oxidative stress and tau hyperphosphorylation, and restore metal dyshomeostasis while demonstrating neuroprotective/neurorestorative effects. These include ladostigil and rasiline.

The subsequent chapter addresses sleep apnea in the elderly and its role in hypoxia, hypoxemia, cerebral hypoperfusion and compromised blood supply, brain hypometabolism in aging and AD. Epidemiological data is employed in this study and the review points to an ever increasing need for researchers to address sleep disorders as the cost of healthcare for AD patients is rising. Chapter 9 of the eBook deals with various natural and synthetic drug therapies and also presents rational guidelines for the prevention of AD. Jellinger presents a timely review on the diagnosis of Alzheimer subtypes – dementias. Morphological dementia is incurable at present, but Jelinger proposes a revision of current diagnostic protocols and frameworks as a basis for early diagnosis and efficient new therapy options against dementias.

In the last chapter of this eBook, the role of various trace metals as cofactors of a poor cognitive function and of an increased risk of dementia leading to AD is reviewed. In particular, this study is a critical analysis of the role played by copper, iron, zinc and aluminum in neurodegeneration.

I hope that readers will find value in these reviews and draw inspiration for conducting further research in the quest for a cure for Alzheimer’s disease and related disorders.

The discovery of new EPO actions beyond the hematopoietic system opened a new field of investigation with these agents. Several molecules have been developed to present the protective action, without the activation of the hematopoietic system. These agents can be potentially used in several diseases of the brain/central and peripheral nervous system, eye, heart and kidney.

This volume of “Frontiers in Drug Discovery” starts with the revision of erythropoiesis (chapter 1), EPO gene regulation (chapter 2), microRNAs and potential contribution to the development of new therapeutic strategies (chapter 3), animal models for studding kidney disease-associated anemia (chapter 4) and risk and benefits of ESA therapy (chapter 5 and 6). In chapter 7 and 8, the biological effects of the new erythropoietic stimulating agents, heparin-binding erythropoietin and of pHBSP, were presented. The remaining chapters of this book show some of the potential applications of erythropoietic stimulating agents.

Atta-ur-Rahman FRS,
UNESCO Science Laureate
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
United Kingdom

List of Contributors

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




Contributor(s):
Chrystelle Mavoungou
Institute of Applied Biotechnology
Faculty for Biotechnology, Biberach University of Applied Science
Karlstrasse 11
Biberach/Riss, D-88400
Germany


Katharina S. Zimmerman
Institute of Applied Biotechnology
Faculty for Biotechnology, Biberach University of Applied Science
Karlstrasse 11
Biberach/Riss, D-88400
Germany


John W. Wright
Departments of Psychology
Veterinary and Comparative Anatomy, Pharmacology, and Physiology
and Programs in Neuroscience and Biotechnology
Washington State University
Pullman
Washington
USA


Joseph W. Harding
Departments of Psychology
Veterinary and Comparative Anatomy, Pharmacology, and Physiology
and Programs in Neuroscience and Biotechnology
Washington State University
Pullman
Washington
USA


Rosaria A. Cavallaro
Department of Surgery “P. Valdoni”
Sapienza University of Rome
Italy


Andrea Fuso
Department of Psychology - Section of Neuroscience
Sapienza University of Rome
Italy


Yasumasa Yoshiyama
Clinical Research Center, Department of Neurology
Chiba East National Hospital
Chiba, Chiba 260-8712
Japan


Zaciragic Asija
Department of Physiology
Medical Faculty University of Sarajevo
Bosnia and Herzegovina


Angela Clifford
SSEHS Loughborough University and Center for Aging Studies Universitas Indonesia
Depok
Indonesia


Jennifer Stock
SSEHS Loughborough University and Center for Aging Studies Universitas Indonesia
Depok
Indonesia


Stephan Bandelow
SSEHS Loughborough University and Center for Aging Studies Universitas Indonesia
Depok
Indonesia


Tri B. Rahardjo
SSEHS Loughborough University and Center for Aging Studies Universitas Indonesia
Depok
Indonesia


Eef Hogervorst
SSEHS Loughborough University and Center for Aging Studies Universitas Indonesia
Depok
Indonesia


Hailin Zheng
Department of Medicinal Chemistry
Intra-cellular Therapies Inc. 3960 Broadway
New York
NY, 10032
USA


Mati Fridkin
Department of Organic Chemistry
The Weizmann Institute of Science
Rehovot, 76100
Israel


Moussa B.H. Youdim
Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases and Department of Pharmacology
Technion-Rappaport Family Faculty of Medicine Haifa
31096, Israel, and Department of Biology
Yonsei World Central University
Seoul
South Korea


Mak A. Daulatzai
Sleep Disorders Group, EEE/MSE
The University of Melbourne
Parkville
Victoria, 3010
Australia


Chuang Wang
Ningbo University School of Medicine
818 Fenghua Road
Ningbo, Zhejiang, 315211
PR China


Rui Wang
Program of Pharmacology
Weill Graduate School of Medical Science
Cornell University
New York
NY, 10021
USA


James M. O’Donnell
Department of Behavioral Medicine and Psychiatry
West Virginia University
Morgantown
WV, 26508
USA


Ying Xu
Department of Behavioral Medicine and Psychiatry
West Virginia University
Morgantown
WV, 26508
USA


Kurt A. Jellinger
Institute of Clinical Neurobiology
Vienna
Austria


Guido Crisponi
Department of Chemistry and Geology
University Campus
Montserrat Cagliari, 09042
Italy


Valeria M. Nurchi
Department of Chemistry and Geology
University Campus
Montserrat Cagliari, 09042
Italy


Daniela Fanni
Department of Surgical Sciences
Sec. Pathology, Via Ospedale 46
Cagliari, 09124
Italy


Clara Gerosa
Department of Surgical Sciences
Sec. Pathology, Via Ospedale 46
Cagliari, 09124
Italy


Sonia Nemolato
Department of Surgical Sciences
Sec. Pathology, Via Ospedale 46
Cagliari, 09124
Italy


Miriam Crespo-Alonso
Department of Chemistry and Geology
University Campus
Montserrat Cagliari, 09042
Italy


Leonardo Toso
Department of Chemistry and Geology
University Campus
Montserrat Cagliari, 09042
Italy


Joanna I. Lachowicz
Department of Chemistry and Geology
University Campus
Montserrat Cagliari, 09042
Italy


Gavino Faa
Department of Surgical Sciences
Sec. Pathology, Via Ospedale 46
Cagliari, 09124
Italy




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