Frontiers in CNS Drug Discovery

Volume 2

by

Atta-ur-Rahman, Iqbal Choudhary

DOI: 10.2174/97816080576721130201
eISBN: 978-1-60805-767-2, 2013
ISBN: 978-1-60805-768-9
ISSN: 1879-6656

  
  




“Frontiers in CNS Drug Discovery” is an eBook series devoted to publishing the latest and the most important advances in Central Nervo...[view complete introduction]
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Table of Contents

Preface , Pp. i-iv (4)

Atta-ur-Rahman
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List of Contributors , Pp. v-vii (3)

Atta-ur-Rahman
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Developing Treatments for Prion Diseases and Implications for Other Protein Misfolding Disorders , Pp. 3-25 (23)

Brian S. Appleby
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Epigenetic Modifications as Novel Targets for Drug Addiction , Pp. 26-42 (17)

Candace R. Lewis and Michael F. Olive
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Manipulation of Endogenous Neural Stem Cells as a Therapeutic Strategy for Neurodegenerative Diseases: Insights from Animal Models , Pp. 43-79 (37)

Anna Patten, Patricia S. Brocardo and Joana M. Gil-Mohapel
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New Therapies for HIV-1-Associated Neurocognitive Disorder (HAND): Animal Models and Gene Delivery of Antioxidant Enzymes by rSV40 , Pp. 80-117 (38)

Jean-Pierre Louboutin and David S. Strayer
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Transient Receptor Potential Ion Channels as Promising Therapeutic Targets: An Overview , Pp. 118-145 (28)

Merab G. Tsagareli
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Antipsychotic Polypharmacy in Schizophrenia, from Empirical Associations to Combined Selective Treatments , Pp. 146-210 (65)

Alessandro De Risio and Davide Carlino
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The Role of Natural Products on the Discovery of New Drug Candidates for Neurogenerative Disorders , Pp. 211-280 (70)

Flávia P.D. Viegas, Rodolfo do C. Maia, Roberta Tesch, Carlos A.M. Fraga and Claudio Viegas
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Flavonoids – Their Preventer and Therapeutic Applications Against Parkinson’s Disease , Pp. 281-311 (31)

Elena González-Burgos and Maria P. Gómez-Serranillos
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Essential Polyunsaturated Fatty Acids as New Treatments for Neurodegenerative Diseases , Pp. 312-333 (22)

Cai Song
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Application of Monoterpenoids and their Derivatives Against CNS Disorders , Pp. 334-380 (47)

Alla V. Pavlova, Konstantin P. Volcho and Tatyana G. Tolstikova
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Use of Zebrafish to Identify New CNS Drugs Acting Through Nicotinic and Dopaminergic Systems , Pp. 381-406 (26)

Robert T. Boyd
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Index , Pp. 407-423 (17)

Atta-ur-Rahman and M. Iqbal Choudhary
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Preface

The present volume 2 of Frontiers in CNS Drug Discovery brings you the latest medical researches on the human Central Nervous System (CNS). Special themes of the 11 chapters in this volume are animal models, natural medicine, mental disorders, and particularly neurodegeneration. Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS) have huge personal, social and economic impacts.

Brian Appleby’s review examines possible treatment targets for protein misfolding disorders, utilizing the knowledge obtained in the field of prion disease. Prion diseases are rapidly progressing neurodegenerative maladies caused by an abnormal conformer of the native prion protein. Even though prion diseases are relatively rare in humans, other neurodegenerative protein misfolding disorders such as Alzheimer’s and Parkinson’s disease are now known to exhibit prion-like behavior and they are likely to benefit from treatments originally designed to deal with prion disease.

Candace Lewis and Foster Olive discuss the relevant epigenetic mechanisms that modulate gene transcription. They review and summarize the existing literature on epigenetic changes that occur after acute and chronic exposure to or selfadministration of alcohol, psychostimulants, opiates, and nicotine, and studies examining the effects of manipulation of epigenetic processes in reward-related brain regions on addiction-like behaviors. The authors also discuss the possible implications of epigenetic factors as predictors of addiction vulnerability prior to drug exposure. Finally, they review findings from preclinical studies on the effects of pharmacological modifiers of epigenetic processes on addiction-related behaviors, and discuss the advantages and disadvantages of developing novel epigenetic-based CNS therapeutics for the treatment of addiction.

The mammalian brain has the capacity to generate new neurons throughout adulthood through a process referred to as adult neurogenesis. Joana M. Gil- Mohapel et al. review the results obtained in rodent models of AD, PD, and HD with regard to therapies aimed at restoring adult neurogenesis and discuss whether such therapies might have therapeutic relevance for the treatment of these devastating neurodegenerative disorders.

HIV-1 is largely impervious to highly active anti-retroviral therapeutic drugs (HAART). Jean-Pierre Louboutin discuss that since curing CNS HIV-1 is currently not possible, limiting the damage caused by the virus may be a useful approach to treatment. The chapter presents models which offer a better understanding of the pathogenesis of HIV-1 in the brain as well as provide new therapeutic avenues.

Transient receptor potential (TRP) ion channels have been extensively studied over the past few years and they are being ardently explored as targets for drug discovery. Recent findings in the field of pain have established a subset of TRP channels that are activated by temperature and are able to initiate sensory nerve impulses following the detection of thermal, as well as mechanical and chemical irritant stimuli. The review by Merab Tsagareli focuses on the latest developments in the TRP ion channel-related area and highlights evidence supporting TRP channels as promising targets for new analgesic drugs at the periphery and central levels and opportunities for therapeutic intervention.

Antipsychotics (APs) have been used for treating schizophrenia and other severe mental disorders for more than fifty years. The aim of the review by Alessandro De Risio and Davide Carlino is to address the boundaries of polypharmacy with APs, from epidemiological features to clinical significance. The chapter looks at prescription patterns, compares the theoretical rationale of monotheraphy and the pharmacokinetic and pharmachodynamic properties of the combined selective associations of two APs. The reasons for using polypharmacy in routine practice are also discussed in the chapter.

The search for new effective chemical entities, capable of acting in diverse biochemical targets, with new mechanisms of action and low toxicity continues to benefit from modern natural products chemistry that can provide active, sophisticated and complex new lead molecules to drug discovery and development. Claudio Viegas-Jr. et al. discuss in their chapter some contributions of natural products chemistry for the discovery of active constituents in plants, ii herbs and extracts to treat senile neurodegenerative disorders, especially for AD and PD, in the period after the 2000s.

Flavonoids are the most abundant plant polyphenolic substances, and they are found in fruits, vegetables and plant-derived beverages. Quite a few natural flavonoids with potential antioxidants and signaling properties are being investigated to identify preventive neuroprotective compounds to stop the progression of PD. The chapter by Elena González-Burgos’ and Pilar Gómez- Serranillos concentrates on the multiple neuroprotection mechanisms of natural flavonoids in PD, covering the latest preclinical in vitro and in vivo PD animal model studies and clinical trials. It provides an overview and the current challenges that may be helpful for future research.

Inflammation plays an important part in the onset and progress of neurodegenerative diseases. Among new products, omega (n)-3 fatty acids have anti-inflammatory and neuroprotective benefits with few side effects. The chapter by Cai Song reviews the new findings from studies in relationship between inflammation and neurodegenerative disease. It also presents the important role of polyunsaturated fatty acids (PUFA) in the brain and the immune system.

Monoterpenoids and their derivatives are important starting materials for the development of new bioactive substances, including drugs. Many of these compounds exhibit feature substantial CNS activities such as antinociceptive, neuroprotective and anticonvulsant. Konstantin Volcho et al. cover the recent literature on monoterpenoids and their derivatives, exhibiting various types of CNS activity in their review.

Use of zebrafish to identify new CNS drugs by high throughput screening is discussed by Thomas Boyd. Many behavioral assays developed in other animals are available in zebrafish, including assays for locomotion, avoidance behaviors, learning, and conditioned place preference. Zebrafish offer an exciting assays for identification of new medicines to treat disorders due to nicotinic cholinergic and dopaminergic dysregulation including nicotine addiction, schizophrenia, Alzheimer's disease and Parkinson's disease.

I am grateful for the timely efforts made by the editorial personnel, especially Mahmood Alam (Director Publications) and Mrs. Sana Mokarram at Bentham Science Publishers.

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

List of Contributors

Editor(s):
Dr. Atta-ur-Rahman



Dr. Iqbal Choudhary





Contributor(s):
Brian S. Appleby
Cleveland Clinic Foundation
Lou Ruvo Center for Brain Health
9500 Euclid Avenue/U10
Cleveland
OH, 44195
USA


Robert T. Boyd
Department of Neuroscience
The Ohio State University College of Medicine, Wexner Medical Center
333 West Tenth Avenue
Columbus
Ohio, 43210
USA


Flávia P.D. Viegas
LFQM – Laboratório de Fitoquímica e Química Medicinal
Instituto de Química,Universidade Federal de Alfenas (UNIFAL-MG)
Alfenas
MG, 37130-000
Brazil


Rodolfo do C. Maia
LASSBio–Laboratório de Avaliação e Síntese de Substâncias Bioativas
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ)
Rio de Janeiro
RJ, 21941-902
Brazil


Roberta Tesch
LASSBio–Laboratório de Avaliação e Síntese de Substâncias Bioativas
Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ)
Rio de Janeiro
RJ, 21941-902
Brazil


Carlos A.M. Fraga
Programa de Pós-Graduação em Farmacologia e Química Medicinal
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ)
Rio de Janeiro
RJ, 21941-902
Brazil


Claudio Viegas-Jr.
Programa de Pós-Graduação em Química
Universidade Federal de Alfenas (UNIFALMG)
Alfenas
MG, 37130-000
Brazil


Cai Song
Research Institute for Marine Nutrition and Drugs
Guangdong Ocean University
China


Candace R. Lewis
Arizona State University
Tempe, AZ 930 S McAllister Ave.
Tempe
AZ, 85287
USA


Michael F. Olive
Arizona State University
Tempe, AZ 930 S McAllister Ave.
Tempe
AZ, 85287
USA


Anna Patten
Division of Medical Sciences, Island Medical Program
University of Victoria
British Columbia
Victoria
Canada


Patricia S. Brocardo
Neuroscience Program
Federal University of Santa Catarina
Florianópolis
Santa Catarina
Brazil


Joana M. Gil-Mohapel
Division of Medical Sciences, Island Medical Program
University of Victoria
Victoria
British Columbia
Canada


Jean-Pierre Louboutin
Department of Pathology
Anatomy and Cell Biology, Thomas Jefferson University
Philadelphia
PA, 19107
USA


David S. Strayer
Department of Pathology
Anatomy and Cell Biology, Thomas Jefferson University
Philadelphia
PA, 19107
USA


Merab G. Tsagareli
Pain Research Group, Department of Neurophysiology
Ivane Beritashvili Center for Experimental Biomedicine
Tbilisi
Georgia


Elena González-Burgos
Department of Pharmacology
Faculty of Pharmacy, University Complutense
Madrid
Spain


Maria P. Gómez-Serranillos
Department of Pharmacology
Faculty of Pharmacy, University Complutense
Madrid
Spain


Alla V. Pavlova
Novosibirsk Institute of Organic Chemistry
Siberian Branch of the Russia Academy of Science
Novosibirsk
Russia


Konstantin P. Volcho
Novosibirsk Institute of Organic Chemistry
Siberian Branch of the Russia Academy of Science
Novosibirsk
Russia


Tatyana G. Tolstikova
Novosibirsk Institute of Organic Chemistry
Siberian Branch of the Russia Academy of Science
Novosibirsk
Russia


Alessandro De Risios
NSH Health Trust No. 10 “Veneto Orientale”
Unit of Psychiatry of Portogruaro
Via Forlanini, 2
Venezia
Portogruaro, 30026
Italia


Davide Carlino
Department of Morphological, Technological and Clinical Science
Clinic of Psychiatry, University of Trieste
Via De Ralli, 5
Trieste, 34128
Italia




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