Polyglutamine disorders preface

(1)

Advances in Experimental Medicine and Biology

Volume 1049

Series editors

Irun R. Cohen, Rehovot, Israel Abel Lajtha, Orangeburg, USA John D. Lambris, Philadelphia, USA Rodolfo Paoletti, Milan, Italy Nima Rezaei, Tehran, Iran

(2)

(3)

Cl

évio Nóbrega

•

Lu

ís Pereira de Almeida

Editors

Polyglutamine Disorders

(4)

Editors Clévio Nóbrega

Department of Biomedical Sciences and Medicine, Centre for Biomedical Research and Algarve Biomedical Center University of Algarve

Faro Portugal

Luís Pereira de Almeida

Center for Neuroscience and Cell Biology and Faculty of Pharmacy

University of Coimbra Coimbra

Portugal

ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology

ISBN 978-3-319-71778-4 ISBN 978-3-319-71779-1 (eBook) https://doi.org/10.1007/978-3-319-71779-1

Library of Congress Control Number: 2017960922

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speciﬁcally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microﬁlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.

The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speciﬁc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional afﬁliations.

Printed on acid-free paper

This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG

(5)

Preface

On Polyglutamine Diseases

Polyglutamine (polyQ) diseases are a group of rare neurodegenerative disorders that share a common genetic cause: they arise as a result of abnormal expansions of CAG trinucleotide sequences occurring at particular genome loci. In contrast with other repeat-related disorders, the repeat-bearing tracts associated with polyQ dis-eases are present at the codifying region of genes, being translated as expanded polyQ tracts in their respective protein products. Although these genes and proteins are otherwise unrelated and share no signiﬁcant homology outside the CAG/polyQ tract, proteins carrying an abnormally expanded polyQ tract tend to aggregate, forming insoluble protein aggregates that constitute a key neuropathological feature of polyQ disorders. The group currently includes nine disorders: Huntington’s disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and six different types of spinocerebellar ataxia: SCA 1, 2, 3, 6, 7, and 17. PolyQ diseases are highly incapacitating and, to this date, no therapy able to modify disease progression is available for any of them.

PolyQ disorders share several features. These include (a) the existence of a positive correlation between the variable CAG repeat number and both the severity and precocity of symptoms; (b) the generational instability in CAG repeat number transmission; and (c) the aforementioned propensity for the protein products to aggregate and to constitute large intracellular multiprotein inclusions that are detected in patients’ neuronal tissue. Despite the genetic cause of polyQ disorders being clearly identiﬁed, the molecular mechanisms involved in their pathogenesis are not fully understood. Though it is frequently accepted that these disorders share common pathogenic mechanisms, the symptoms and the regional patterns of neu-rodegeneration are not shared among disorders. Taken together, the similarities and differences existing in this group of disorders suggest that the search for disease mechanisms and putative therapeutic strategies will beneﬁt from an integrative view that conjugates common factors and motifs with the particularities of each polyQ disease.

(6)

For this book entitled Polyglutamine Disorders, we have gathered many of the main experts around the world in theﬁeld, whom we would like to acknowledge for their work and collaboration, providing a state-of-the-art revision about several aspects of the different polyQ diseases. The book addresses the molecular mech-anisms described to underlie disease pathogenesis, the animal models developed to study these diseases and, importantly, the advanced therapeutic strategies being investigated for these disorders.

Coimbra, Portugal Clévio Nóbrega

January 2018 Luís Pereira de Almeida

(7)