Author
Pedro Merino
Universidad de Zaragoza
Departamento de Qumica Orgánica
Campus San Francisco
Zaragoza
E‐50009 Aragón
Spain
Cover Images Images were kindly provided by Pedro Merino (University of Zaragoza, Spain)
All books published by Wiley‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
Library of Congress Card No.:
applied for
British Library Cataloguing‐in‐Publication Data
A catalogue record for this book is available from the British Library.
Bibliographic information published by
the Deutsche Nationalbibliothek
The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d‐nb.de>.
© 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978‐3‐527‐34424‐6
ePDF ISBN: 978‐3‐527‐81343‐8
ePub ISBN: 978‐3‐527‐81345‐2
oBook ISBN: 978‐3‐527‐81342‐1
Neurodegeneration is the progressive loss of structure or function of neurons and causes many neurodegenerative disorders. Diseases affecting the central nervous system (CNS) that implicate directly not neurons (e.g. multiple sclerosis) or those in which neurons die because of acute episodes (infections, hypoxia, edema, trauma, etc.) are not considered neurodegenerative. Several types of neurodegenerative diseases have been reported, and many of them have a clinic and pathologic overlap. In general, they are differentiated by the predominant region affected in the brain although a more detailed classification is made on the basis of symptoms and predominant clinical features [1].
The main neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Lewis body dementia (LBD), and amyotrophic lateral sclerosis (ALS). Almost all neurodegenerative disorders have an origin unknown, and only devastating effects are observed. Neurodegenerative disorders are age associated, and the etiology of neurodegenerative diseases regarding the role of the different risk factors, especially positive family history, unhealthy lifestyle, and toxic environment, is still under debate [2]. With few exceptions, a combination of both causes (family story and toxic environment) should be considered. Recent advances on mechanisms underlying neurodegenerative diseases focus on neurotoxicity, neurovascular dysfunction, accumulation of misfolded proteins, and selective vulnerability of certain neurons and other brain cells such as microglia [3].
Currently, treatment of symptoms is the only therapeutic approach to neurodegenerative diseases. Prior to search a cure, it is necessary to understand the chemical processes involved in the diseases, and for that goal, the molecular structures involved in the affected brain areas also need to be identified. This book focuses on the main actors of CNS involved in neurodegenerative disorders at a molecular level with great emphasis on structural aspects and modes of action.
The first part introduces the neurotransmitter systems. Clinical aspects are reduced to a minimum since there are many exclusive books and treatises on this topic. In this respect, this part contains an introduction on the neurotransmitter system including a general explanation of the synapse and a description of the main structures involved in neurotransmission that can be considered therapeutic targets for neurodisorders, including receptors and transporters. Pharmacological features (of special interest in characterization of receptors) are not considered in detail because books and encyclopedia collecting all details for each receptor are available. Neurotransmitter systems are deeply discussed to give the reader a general overview. All aspects are not treated in detail, because several volumes need to be devoted for those topics alone.
The second part presents molecular and chemical aspects directly involved in neurodegeneration including metabolism of neurotransmitters, enzymes processing neurotransmitters, protein misfolding, and therapeutic agents.