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Melanocortins Multiple Actions and TherapeuticPotential

:	Anna Catania
:	Anna Catania
:	Melanocortins Multiple Actions and TherapeuticPotential
:	Springer-Verlag
:	9781441963543
:	1
:	CHF 132.90
:

:	Nichtklinische Fächer
:	English

:	153
:	Wasserzeichen
:	PC/MAC/eReader/Tablet
:	PDF

It is clear that the melanocortins are of immense academic interest. Further, these molecules have remarkable potential as pharmaceutical agents for treatment of multiple human and veterinary disorders and diseases. The evidence to support academic interest and clinical applications lies in significant part within the chapters of this book, chapters written by noted experts in the field who have worked diligently to understand the molecules and to move them toward clinical applications. I personally believe that the - MSH molecule and its derivatives will be used as routine therapeutics in the very near future. My belief is so strong that I left academia to form a company based on -MSH analogs and have caused millions of dollars to be spent on melanocortin research. Now why would a sane professor pick up such a challenge and enter business, an essential step toward any clinical application? It is the - MSH story that drove me. Consider that - MSH occurs in exactly the same amino acid sequence in humans and in the sea lamprey, an organism unchanged since its appearance during the Pennsylvanian period of the Paleozoic era (about 300 million years ago-way before dinosaurs were to be considered). There is unpublished evidence that the stability of the molecule can be traced back a half billion years. Frankly, I believe that the molecule existed even when single cells began to live together.

ANNA CATA NIA, MD, PhD is a director of Center for Preclinical Investigation at Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy. She received her degree in Medicine and Surgery at the University of Milan and postdoctoral degree in Endocrinology and Metabolism at the University of Genoa, Italy. For over a decade she has been visiting scientist at The University of Texas Southwestern Medical Center at Dallas, Texas. During the past 20 years, her research activity has been focused on molecular biology and preclinical testing of melanocortins.

	Title Page	3
	Copyright Page	4
	DEDICATION	5
	FOREWORD	6
	PREFACE	8
	ABOUT THE EDITOR...	10
	PARTICIPANTS	11
	Table of Contents	15
	Chapter 1 Structure-Activity Relationships (SAR)of Melanocortin and Agouti-Related(AGRP) Peptides	19
	Introduction	19
	Structure and Chemistry of Melanocortin Peptides	20
	Structure-Activity Relationships (SAR)	20
	Linear Melanocortin Peptides	21
	a-MSH	21
	Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2	22
	N-Terminus Modifications	24
	ß-MSH	26
	.MSH	26
	ACTH	27
	NDP-MSH	27
	SAR of Cyclic Melanocortin Peptides	27
	Agouti-Related Protein (AGRP)	29
	AGRP Structure	29
	AGRP SAR	29
	Development of Chimeric Peptide Analogues	31
	Conclusion	32
	References	32
	Chapter 2 Melanocortin Signalling Mechanisms	37
	Introduction	37
	Melanocortin Receptors	38
	Melanocortins and Pigmentation	39
	Melanocortin Anti-Inflammatory and Immunomodulatory Roles	40
	Intracellular Signalling of Melanocortin Peptides	40
	Melanocortin Receptor Antagonists and Agonists	43
	Conclusion	44
	References	44
	Chapter 3 Distribution and Function of Melanocortin Receptors within the Brain	47
	Introduction	47
	MC1R Is Expressed in the Periaqueductal Gray and the MC1R Regulates Pain and Analgesia	48
	MC2R Is Expressed in Teleost Fish Brain and Fetal Mouse Brain, but Not in Adult Mammalian Brain	49
	MC3R Is Specifically Expressed in Hypothalamus and the LimbicSystem Where Its Functions Are Not Clearly Understood	49
	Adult Brain	49
	Fetal and Postnatal Brain	50
	Functions for MC3R in Brain	51
	MC4R Is Expressed in Distinct Nuclei in Every Region of the BrainReflecting It s Many Diverse Functions in the Brain	52
	Adult Brain	52
	Fetal and Postnatal Brain	53
	Functions for MC4R in the Brain	53
	MC5R Expression and Function in the Brain Is Unclear	56
	Melanocortin Receptor Accessory Proteins (MRAPs)	57
	Conclusion	57
	References	60
	Chapter 4 Drugs, Exercise, and the Melanocortin-4 Receptor Different Means, Same Ends: Treating Obesity	67
	Introduction	67
	Melanocortins	68
	Exercise	72
	Conclusion	75
	References	75
	Chapter 5 Melanocortins in Brain Inflammation: The Role of Melanocortin Receptor Subtypes	79
	Introduction	79
	Distribution of MC Expressing Neurons and MC Receptors in the Brain	79
	MCR Subtypes and Brain Inflammation	81
	Main Intracellular Signalling Pathways of MC Receptors	82
	Potential Therapeutic Applications of MC Receptor Subtype Selective Compounds	84
	Conclusion	86
	References	86
	Chapter 6 Melanocortins and the Cholinergic Anti-Inflammatory Pathway	89
	Introduction	89
	The Inflammatory Reflex	90
	Antishock Effects of Melanocortins	91
	Melanocortins Reverse Circulatory Shock through Activationof the Cholinergic Anti-Inflammatory Pathway	92
	Protective Effect of M