Polyglutamine Ataxias: Our Current Molecular Understanding and What the Future Holds for Antisense Therapies

From Genotype to Phenotype: Expanding the Clinical Spectrum of CACNA1A Variants in the Era of Next Generation Sequencing

(2021) Elisabetta Indelicato et al.   Frontiers in Neurology

Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias

(2021) Ricardo Afonso-Reis et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

SCA7 mouse cerebellar pathology reveals preferential downregulation of key Purkinje cell-identity genes and shared disease signature with SCA1 and SCA2.

(2021) Anna Niewiadomska-Cimicka et al.   JOURNAL OF NEUROSCIENCE

Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3

(2021) Jennifer Faber et al.   MOVEMENT DISORDERS

Failure of genetic therapies for Huntington’s devastates community

(2021) Diana Kwon   NATURE

Antisense technology: an overview and prospectus

(2021) Stanley T. Crooke et al.   NATURE REVIEWS DRUG DISCOVERY

The Evolution of Antisense Oligonucleotide Chemistry—A Personal Journey

(2021) Sudhir Agrawal   Biomedicines

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients

(2020) Luis Velázquez-Pérez et al.   CEREBELLUM

Founder Effects of Spinocerebellar Ataxias in the American Continents and the Caribbean

(2020) Roberto Rodríguez-Labrada et al.   CEREBELLUM

Interferon mediated neuroinflammation in polyglutamine disease is not caused by RNA toxicity

(2020) Aksheev Bhambri et al.   Cell Death & Disease

Neuroimaging Spectrum at Pre-, Early, and Late Symptomatic Stages of SCA17 Mice

(2020) Chiao-Chi Chen et al.   CEREBELLUM

Antisense targeting of decoy exons can reduce intron retention and increase protein expression in human erythroblasts

(2020) Marilyn K Parra et al.   RNA

Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3

(2020) Yi-Chu Du et al.   CEREBELLUM

Viltolarsen: First Approval

(2020) Sohita Dhillon   DRUGS

Therapeutic antisense oligonucleotides for movement disorders

(2020) Epaminondas Doxakis   MEDICINAL RESEARCH REVIEWS

Antisense oligonucleotide modulation of non-productive alternative splicing upregulates gene expression

(2020) Kian Huat Lim et al.   Nature Communications

The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias

(2020) Davin Lee et al.   Frontiers in Neuroscience

Nonsequential Splicing Events Alter Antisense-Mediated Exon Skipping Outcome in COL7A1

(2020) Kristin A. Ham et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Direct evidence that Ataxin-2 is a translational activator mediating cytoplasmic polyadenylation

(2020) Hiroto Inagaki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Simultaneous ALS and SCA2 associated with an intermediate-length ATXN2 CAG-repeat expansion

(2020) Helia Ghahremani Nezhad et al.   Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias

(2019) Ronald A.M. Buijsen et al.   Neurotherapeutics

Therapeutic Antisense Oligonucleotides Are Coming of Age

(2019) C. Frank Bennett   Annual Review of Medicine

Shaoyao Gancao Tang (SG-Tang), a formulated Chinese medicine, reduces aggregation and exerts neuroprotection in spinocerebellar ataxia type 17 (SCA17) cell and mouse models

(2019) Chiung-Mei Chen et al.   Aging-US

Suppression of the yeast elongation factor Spt4 ortholog reduces expanded SCA36 GGCCUG repeat aggregation and cytotoxicity

(2019) Natsumi Furuta et al.   BRAIN RESEARCH

Nucleic Acid Therapeutics for Neurological Diseases

(2019) Jonathan K. Watts et al.   Neurotherapeutics

Molecular Mechanisms and Therapeutics for SCA17

(2019) Qiong Liu et al.   Neurotherapeutics

Suppression of Mutant Protein Expression in SCA3 and SCA1 Mice Using a CAG Repeat-Targeting Antisense Oligonucleotide

(2019) Eleni Kourkouta et al.   Molecular Therapy-Nucleic Acids

Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review

(2019) Martina Rekatsina et al.   ADVANCES IN THERAPY

Systematic Approach to Developing Splice Modulating Antisense Oligonucleotides

(2019) May Aung-Htut et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Removal of the Polyglutamine Repeat of Ataxin-3 by Redirecting pre-mRNA Processing

(2019) Craig S. McIntosh et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Pueraria lobata and Daidzein Reduce Cytotoxicity by Enhancing Ubiquitin-Proteasome System Function in SCA3-iPSC-Derived Neurons

(2019) I-Cheng Chen et al.   Oxidative Medicine and Cellular Longevity

Reduction of integrin alpha 4 activity through splice modulating antisense oligonucleotides

(2019) May T. Aung-Htut et al.   Scientific Reports

Pathogenesis of SCA3 and implications for other polyglutamine diseases

(2019) Hayley S. McLoughlin et al.   NEUROBIOLOGY OF DISEASE

Consequences of Making the Inactive Active Through Changes in Antisense Oligonucleotide Chemistries

(2019) Khine Zaw et al.   Frontiers in Genetics

Oligonucleotide therapy mitigates disease in Spinocerebellar Ataxia Type 3 mice

(2018) Hayley S. McLoughlin et al.   ANNALS OF NEUROLOGY

Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity

(2018) Y. Torres-Ramos et al.   CEREBELLUM

Sequencing analysis of the SCA6 CAG expansion excludes an influence of repeat interruptions on disease onset

(2018) Sarah Wiethoff et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Why do so many genetic insults lead to Purkinje Cell degeneration and spinocerebellar ataxia?

(2018) Miaozhen Huang et al.   NEUROSCIENCE LETTERS

Antisense Oligonucleotide-Mediated Terminal Intron Retention of the SMN2 Transcript

(2018) Loren L. Flynn et al.   Molecular Therapy-Nucleic Acids

Purkinje cell COX deficiency and mtDNA depletion in an animal model of spinocerebellar ataxia type 1

(2018) Michela Ripolone et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Spinocerebellar ataxias: prospects and challenges for therapy development

(2018) Tetsuo Ashizawa et al.   Nature Reviews Neurology

Vulnerability of frontal brain neurons for the toxicity of expanded ataxin-3

(2018) Jana Schmidt et al.   HUMAN MOLECULAR GENETICS

Antisense oligonucleotides targeting mutant Ataxin-7 restore visual function in a mouse model of spinocerebellar ataxia type 7

(2018) Chenchen Niu et al.   Science Translational Medicine

Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters

(2017) Nanna Cornelius et al.   MITOCHONDRION

LSM12 and ME31B/DDX6 Define Distinct Modes of Posttranscriptional Regulation by ATAXIN-2 Protein Complex in Drosophila Circadian Pacemaker Neurons

(2017) Jongbo Lee et al.   MOLECULAR CELL

Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice

(2017) Lindsay A. Becker et al.   NATURE

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2

(2017) Daniel R. Scoles et al.   NATURE

Polyglutamine tracts regulate beclin 1-dependent autophagy

(2017) Avraham Ashkenazi et al.   NATURE

The chemical evolution of oligonucleotide therapies of clinical utility

(2017) Anastasia Khvorova et al.   NATURE BIOTECHNOLOGY

Antisense oligonucleotides: the next frontier for treatment of neurological disorders

(2017) Carlo Rinaldi et al.   Nature Reviews Neurology

Polyglutamine spinocerebellar ataxias — from genes to potential treatments

(2017) Henry L. Paulson et al.   NATURE REVIEWS NEUROSCIENCE

Deregulation of autophagy in postmortem brains of Machado-Joseph disease patients

(2017) Annie Sittler et al.   NEUROPATHOLOGY

Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials

(2017) Li Fan et al.   PHARMACOLOGICAL RESEARCH

Unraveling the Role of Ataxin-2 in Metabolism

(2017) Sara Carmo-Silva et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

The Truncated C-terminal Fragment of Mutant ATXN3 Disrupts Mitochondria Dynamics in Spinocerebellar Ataxia Type 3 Models

(2017) Jung-Yu Hsu et al.   Frontiers in Molecular Neuroscience

The Ubiquitination, Disaggregation and Proteasomal Degradation Machineries in Polyglutamine Disease

(2017) Samir R. Nath et al.   Frontiers in Molecular Neuroscience

Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch

(2017) E. F. E. Kuiper et al.   Frontiers in Neuroscience

Ataxin-2: From RNA Control to Human Health and Disease

(2017) Lauren Ostrowski et al.   Genes

Antisense Oligonucleotide-Mediated Removal of the Polyglutamine Repeat in Spinocerebellar Ataxia Type 3 Mice

(2017) Lodewijk J.A. Toonen et al.   Molecular Therapy-Nucleic Acids

Peripheral Oxidative Stress Biomarkers in Spinocerebellar Ataxia Type 3/Machado–Joseph Disease

(2017) Adriano M. de Assis et al.   Frontiers in Neurology

Protein misfolding in neurodegenerative diseases: implications and strategies

(2017) Patrick Sweeney et al.   Translational Neurodegeneration

DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

(2016) Conceição Bettencourt et al.   ANNALS OF NEUROLOGY

RNA toxicity induced by expanded CAG repeats in Huntington's disease

(2016) Eulàlia Martí   BRAIN PATHOLOGY

Impact of Ataxin-2 knock out on circadian locomotor behavior and PER immunoreaction in the SCN of mice

(2016) Martina Pfeffer et al.   CHRONOBIOLOGY INTERNATIONAL

Genetically modified rodent models of SCA17

(2016) Yiting Cui et al.   JOURNAL OF NEUROSCIENCE RESEARCH

Episodic ataxia and SCA6 within the same family due to the D302N CACNA1A gene mutation

(2016) Luca Pradotto et al.   JOURNAL OF THE NEUROLOGICAL SCIENCES

Ataxin-2 (Atxn2)-Knock-Out Mice Show Branched Chain Amino Acids and Fatty Acids Pathway Alterations

(2016) David Meierhofer et al.   MOLECULAR & CELLULAR PROTEOMICS

Polyglutamine aggregation in Huntington's disease and spinocerebellar ataxia type 3: similar mechanisms in aggregate formation

(2015) K. Seidel et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation

(2015) Paola Giunti et al.   Frontiers in Cellular Neuroscience

Repeat Associated Non-AUG Translation (RAN Translation) Dependent on Sequence Downstream of the ATXN2 CAG Repeat

(2015) Daniel R. Scoles et al.   PLoS One

Polyglutamine (PolyQ) Diseases: Genetics to Treatments

(2014) Hueng-Chuen Fan et al.   CELL TRANSPLANTATION

Trinucleotide expansion in disease: why is there a length threshold?

(2014) Do-Yup Lee et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

HMGB1 facilitates repair of mitochondrial DNA damage and extends the lifespan of mutant ataxin-1 knock-in mice

(2014) H. Ito et al.   EMBO Molecular Medicine

A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression

(2014) Katrin Bürk et al.   European Journal of Medical Genetics

Loss of Drosophila Ataxin-7, a SAGA subunit, reduces H2B ubiquitination and leads to neural and retinal degeneration

(2014) R. D. Mohan et al.   GENES & DEVELOPMENT

Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies

(2013) Melvin M. Evers et al.   MOLECULAR NEUROBIOLOGY

Silencing Mutant ATXN3 Expression Resolves Molecular Phenotypes in SCA3 Transgenic Mice

(2013) Edgardo Rodríguez-Lebrón et al.   MOLECULAR THERAPY

RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1

(2013) Megan S. Keiser et al.   NEUROBIOLOGY OF DISEASE

Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: Removal of the CAG containing exon

(2013) Melvin M. Evers et al.   NEUROBIOLOGY OF DISEASE

Brain pathology of spinocerebellar ataxias

(2012) Kay Seidel et al.   ACTA NEUROPATHOLOGICA

Calcium channels and migraine

(2012) Daniela Pietrobon   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Alternative splicing: Functional diversity among voltage-gated calcium channels and behavioral consequences

(2012) Diane Lipscombe et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

Neuronal P/Q-type calcium channel dysfunction in inherited disorders of the CNS

(2012) Sanjeev Rajakulendran et al.   Nature Reviews Neurology

Patterns of Mitochondrial DNA Damage in Blood and Brain Tissues of a Transgenic Mouse Model of Machado-Joseph Disease

(2012) Nadiya Kazachkova et al.   Neurodegenerative Diseases

Sustained Therapeutic Reversal of Huntington's Disease by Transient Repression of Huntingtin Synthesis

(2012) Holly B. Kordasiewicz et al.   NEURON

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation

(2012) José Barros et al.   JAMA Neurology

Compromised mitochondrial complex II in models of Machado–Joseph disease

(2011) Mário N. Laço et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Overexpression of the autophagic beclin-1 protein clears mutant ataxin-3 and alleviates Machado–Joseph disease

(2011) Isabel Nascimento-Ferreira et al.   BRAIN

Ataxin-1 and Brother of ataxin-1 are components of the Notch signalling pathway

(2011) Xin Tong et al.   EMBO REPORTS

Ataxin-2 repeat-length variation and neurodegeneration

(2011) O. A. Ross et al.   HUMAN MOLECULAR GENETICS

Mutant CAG repeats of Huntingtin transcript fold into hairpins, form nuclear foci and are targets for RNA interference

(2011) Mateusz de Mezer et al.   NUCLEIC ACIDS RESEARCH

CAG repeats mimic CUG repeats in the misregulation of alternative splicing

(2011) Agnieszka Mykowska et al.   NUCLEIC ACIDS RESEARCH

Autophagy and polyglutamine diseases

(2011) Maria Jimenez-Sanchez et al.   PROGRESS IN NEUROBIOLOGY

Nuclear Aggregation of Polyglutamine-expanded Ataxin-3

(2010) Peter Breuer et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond

(2010) Alexandra Durr   LANCET NEUROLOGY

Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

(2010) Andrew C. Elden et al.   NATURE

Repeat expansion disease: progress and puzzles in disease pathogenesis

(2010) Albert R. La Spada et al.   NATURE REVIEWS GENETICS

Splice Isoforms of the Polyglutamine Disease Protein Ataxin-3 Exhibit Similar Enzymatic yet Different Aggregation Properties

(2010) Ginny Marie Harris et al.   PLoS One

The (CAG)n tract of Machado–Joseph Disease gene (ATXN3): a comparison between DNA and mRNA in patients and controls

(2009) Conceição Bettencourt et al.   EUROPEAN JOURNAL OF HUMAN GENETICS

Increased transcript diversity: novel splicing variants of Machado–Joseph Disease gene (ATXN3)

(2009) Conceição Bettencourt et al.   NEUROGENETICS

Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin

(2009) Luis Velázquez Pérez et al.   NEUROSCIENCE LETTERS

Dissociated Fear and Spatial Learning in Mice with Deficiency of Ataxin-2

(2009) Duong P. Huynh et al.   PLoS One

The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases

(2008) K. Usdin   GENOME RESEARCH

RNA toxicity is a component of ataxin-3 degeneration in Drosophila

(2008) Ling-Bo Li et al.   NATURE

Intrafamilial variability of Parkinson phenotype in SCAs: Novel cases due to SCA2 and SCA3 expansions

(2008) M.P. Socal et al.   PARKINSONISM & RELATED DISORDERS

Spinocerebellar ataxia type 6 knockin mice develop a progressive neuronal dysfunction with age-dependent accumulation of mutant CaV2.1 channels

(2008) K. Watase et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA