Polyglutamine Disorders 1st Ed. 2018

This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies’ development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington’s disease (HD); spinal–bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression. Front Matter ....Pages i-viii Clinical Features of Huntington’s Disease (Rhia Ghosh, Sarah J. Tabrizi)....Pages 1-28 Genetic Rodent Models of Huntington Disease (J. Stricker-Shaver, A. Novati, L. Yu-Taeger, H. P. Nguyen)....Pages 29-57 Mitochondrial Dysfunction in Huntington’s Disease (Catarina Carmo, Luana Naia, Carla Lopes, A. Cristina Rego)....Pages 59-83 RNA Related Pathology in Huntington’s Disease (Andreas Neueder, Gillian P. Bates)....Pages 85-101 X-Linked Spinal and Bulbar Muscular Atrophy: From Clinical Genetic Features and Molecular Pathology to Mechanisms Underlying Disease Toxicity (Constanza J. Cortes, Albert R. La Spada)....Pages 103-133 Spinocerebellar Ataxia Type 1: Molecular Mechanisms of Neurodegeneration and Preclinical Studies (Judit M. Pérez Ortiz, Harry T. Orr)....Pages 135-145 Spinocerebellum Ataxia Type 6: Molecular Mechanisms and Calcium Channel Genetics (Xiaofei Du, Christopher Manuel Gomez)....Pages 147-173 Spinocerebellar Ataxia Type 2 (Daniel R. Scoles, Stefan M. Pulst)....Pages 175-195 Molecular Mechanisms and Therapeutic Strategies in Spinocerebellar Ataxia Type 7 (Alice Karam, Yvon Trottier)....Pages 197-218 Spinocerebellar Ataxia Type 17 (SCA17) (Yasuko Toyoshima, Hitoshi Takahashi)....Pages 219-231 The Neuropathology of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (Arnulf H. Koeppen)....Pages 233-241 Origins and Spread of Machado-Joseph Disease Ancestral Mutations Events (Sandra Martins, Jorge Sequeiros)....Pages 243-254 Clinical Features of Machado-Joseph Disease (Nuno Mendonça, Marcondes C. França Jr., António Freire Gonçalves, Cristina Januário)....Pages 255-273 Polyglutamine-Independent Features in Ataxin-3 Aggregation and Pathogenesis of Machado-Joseph Disease (Ana Luisa Carvalho, Alexandra Silva, Sandra Macedo-Ribeiro)....Pages 275-288 Animal Models of Machado-Joseph Disease (Jana Schmidt, Thorsten Schmidt)....Pages 289-308 Towards the Identification of Molecular Biomarkers of Spinocerebellar Ataxia Type 3 (SCA3)/Machado-Joseph Disease (MJD) (Manuela Lima, Mafalda Raposo)....Pages 309-319 Planning Future Clinical Trials for Machado-Joseph Disease (Jonas Alex Morales Saute, Laura Bannach Jardim)....Pages 321-348 Molecular Mechanisms and Cellular Pathways Implicated in Machado-Joseph Disease Pathogenesis (Clévio Nóbrega, Ana Teresa Simões, Joana Duarte-Neves, Sónia Duarte, Ana Vasconcelos-Ferreira, Janete Cunha-Santos et al.)....Pages 349-367 Pharmacological Therapies for Machado-Joseph Disease (Sara Duarte-Silva, Patrícia Maciel)....Pages 369-394 Gene Therapies for Polyglutamine Diseases (Carlos A. Matos, Vítor Carmona, Udaya-Geetha Vijayakumar, Sara Lopes, Patrícia Albuquerque, Mariana Conceição et al.)....Pages 395-438 Stem Cell-Based Therapies for Polyglutamine Diseases (Liliana S. Mendonça, Isabel Onofre, Catarina Oliveira Miranda, Rita Perfeito, Clévio Nóbrega, Luís Pereira de Almeida)....Pages 439-466 Back Matter ....Pages 467-469