Protein Aggregation Inhibitors as Disease-Modifying Therapies for Polyglutamine Diseases

Arginine is a disease modifier for polyQ disease models that stabilizes polyQ protein conformation

(2020) Eiko N Minakawa et al.   BRAIN

Targeting Huntingtin Expression in Patients with Huntington’s Disease

(2019) Sarah J. Tabrizi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of Arginine Ethyl Ester as Polyglutamine Aggregation Inhibitor: Conformational Transitioning of Huntingtin N-Terminus Augments Aggregation Suppression

(2019) Virender Singh et al.   ACS Chemical Neuroscience

Molecular mechanism of the inhibition of TDP-43 amyloidogenesis by QBP1

(2019) Miguel Mompeán et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Lipid Membranes Influence the Ability of Small Molecules To Inhibit Huntingtin Fibrillization

(2019) Maryssa Beasley et al.   BIOCHEMISTRY

Optimizing intracellular antibodies (intrabodies/nanobodies) to treat neurodegenerative disorders

(2019) Anne Messer et al.   NEUROBIOLOGY OF DISEASE

Nanoscopic Insights of Amphiphilic Peptide against the Oligomer Assembly Process to Treat Huntington's Disease

(2019) Ruei‐Yu He et al.   Advanced Science

Oligonucleotide therapy mitigates disease in Spinocerebellar Ataxia Type 3 mice

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

Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein

(2018) Sumanta Ghosh et al.   Scientific Reports

Ethical Challenges Confronted When Providing Nusinersen Treatment for Spinal Muscular Atrophy

(2018) Alyssa M. Burgart et al.   JAMA Pediatrics

Therapeutic regimen of l-arginine for MELAS: 9-year, prospective, multicenter, clinical research

(2018) Yasutoshi Koga et al.   JOURNAL OF NEUROLOGY

Biodegradable Nanoparticles Containing Mechanism Based Peptide Inhibitors Reduce Polyglutamine Aggregation in Cell Models and Alleviate Motor Symptoms in a Drosophila Model of Huntington’s Disease

(2018) Abhayraj S. Joshi et al.   ACS Chemical Neuroscience

Brain-Targeting Delivery of Two Peptidylic Inhibitors for Their Combination Therapy in Transgenic Polyglutamine Disease Mice via Intranasal Administration

(2018) Mengbi Yang et al.   MOLECULAR PHARMACEUTICS

Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects

(2018) Min Jee Kwon et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Huntingtin suppression restores cognitive function in a mouse model of Huntington’s disease

(2018) Amber L. Southwell et al.   Science Translational Medicine

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2

(2017) Daniel R. Scoles et al.   NATURE

Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases

(2017) Kathleen M. Schoch et al.   NEURON

Spatiotemporal Proteomic Profiling of Huntington’s Disease Inclusions Reveals Widespread Loss of Protein Function

(2017) Fabian Hosp et al.   Cell Reports

Evaluation of Antisense Oligonucleotides Targeting ATXN3 in SCA3 Mouse Models

(2017) Lauren R. Moore et al.   Molecular Therapy-Nucleic Acids

The expanded CAG repeat in the huntingtin gene as target for therapeutic RNA modulation throughout the HD mouse brain

(2017) Nicole A. Datson et al.   PLoS One

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

(2017) Debra J. Skene et al.   Scientific Reports

Targeting CAG repeat RNAs reduces Huntington’s disease phenotype independently of huntingtin levels

(2016) Laura Rué et al.   JOURNAL OF CLINICAL INVESTIGATION

Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors

(2016) Yujin E. Kim et al.   MOLECULAR CELL

Recommendations for the Management of Strokelike Episodes in Patients With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Strokelike Episodes

(2016) Mary Kay Koenig et al.   JAMA Neurology

Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy

(2015) Kentaro Sahashi et al.   HUMAN MOLECULAR GENETICS

Peptide-Based Therapeutic Approaches for Treatment of the Polyglutamine Diseases

(2014) Toshihide Takeuchi et al.   CURRENT MEDICINAL CHEMISTRY

Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity

(2014) Xin Sun et al.   HUMAN MOLECULAR GENETICS

Epigallocatechin-3-gallate and tetracycline differently affect ataxin-3 fibrillogenesis and reduce toxicity in spinocerebellar ataxia type 3 model

(2014) Marcella Bonanomi et al.   HUMAN MOLECULAR GENETICS

The therapeutic potential of chemical chaperones in protein folding diseases

(2014) Leonardo Cortez et al.   Prion

Peripheral Androgen Receptor Gene Suppression Rescues Disease in Mouse Models of Spinal and Bulbar Muscular Atrophy

(2014) Andrew P. Lieberman et al.   Cell Reports

Intravitreal Administration of HA-1077, a ROCK Inhibitor, Improves Retinal Function in a Mouse Model of Huntington Disease

(2013) Mei Li et al.   PLoS One

Identification of Novel Potentially Toxic Oligomers Formedin Vitrofrom Mammalian-derived Expanded huntingtin Exon-1 Protein

(2012) Leslie G. Nucifora et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Creatine metabolism in urea cycle defects

(2012) Sara Boenzi et al.   JOURNAL OF INHERITED METABOLIC DISEASE

Physical Chemistry of Polyglutamine: Intriguing Tales of a Monotonous Sequence

(2012) Ronald Wetzel   JOURNAL OF MOLECULAR BIOLOGY

Methylene Blue Modulates Huntingtin Aggregation Intermediates and Is Protective in Huntington's Disease Models

(2012) E. M. Sontag et al.   JOURNAL OF NEUROSCIENCE

Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington's disease

(2012) Miriam A Hickey et al.   Molecular Neurodegeneration

Drug repositioning for Alzheimer's disease

(2012) Anne Corbett et al.   NATURE REVIEWS DRUG DISCOVERY

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

(2012) Holly B. Kordasiewicz et al.   NEURON

Curcumin Prevents Formation of Polyglutamine Aggregates by Inhibiting Vps36, a Component of the ESCRT-II Complex

(2012) Meenakshi Verma et al.   PLoS One

Expanded Polyglutamine-Binding Peptoid as a Novel Therapeutic Agent for Treatment of Huntington's Disease

(2011) Xuesong Chen et al.   CHEMISTRY & BIOLOGY

An aggregation sensing reporter identifies leflunomide and teriflunomide as polyglutamine aggregate inhibitors

(2011) Rodrigo A. Fuentealba et al.   HUMAN MOLECULAR GENETICS

The Rate of PolyQ-Mediated Aggregation Is Dramatically Affected by the Number and Location of Surrounding Domains

(2011) Amy L. Robertson et al.   JOURNAL OF MOLECULAR BIOLOGY

Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin

(2011) Jeffrey B Carroll et al.   MOLECULAR THERAPY

Identifying polyglutamine protein species in situ that best predict neurodegeneration

(2011) Jason Miller et al.   Nature Chemical Biology

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

(2011) Amber L. Southwell et al.   PLoS One

RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform

(2010) C. Frank Bennett et al.   Annual Review of Pharmacology and Toxicology

Essential Role of Coiled Coils for Aggregation and Activity of Q/N-Rich Prions and PolyQ Proteins

(2010) Ferdinando Fiumara et al.   CELL

Mutant Huntingtin Fragments Form Oligomers in a Polyglutamine Length-dependent Mannerin Vitroandin Vivo

(2010) Justin Legleiter et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Tracking Mutant Huntingtin Aggregation Kinetics in Cells Reveals Three Major Populations That Include an Invariant Oligomer Pool

(2010) Maya A. Olshina et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Early or Late-Stage Anti-N-Terminal Huntingtin Intrabody Gene Therapy Reduces Pathological Features in B6.HDR6/1 Mice

(2010) Abigail Snyder-Keller et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease

(2009) Kirupa Sathasivam et al.   HUMAN MOLECULAR GENETICS

Intrabody Gene Therapy Ameliorates Motor, Cognitive, and Neuropathological Symptoms in Multiple Mouse Models of Huntington's Disease

(2009) A. L. Southwell et al.   JOURNAL OF NEUROSCIENCE

Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs

(2009) Jiaxin Hu et al.   NATURE BIOTECHNOLOGY

Y-27632 improves rotarod performance and reduces huntingtin levels in R6/2 mice

(2009) Mei Li et al.   NEUROBIOLOGY OF DISEASE

Surface plasmon resonance characterization of specific binding of polyglutamine aggregation inhibitors to the expanded polyglutamine stretch

(2008) Yuma Okamoto et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Structure–activity relationship study on polyglutamine binding peptide QBP1

(2008) Kenji Tomita et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin

(2008) Chuan-En Wang et al.   JOURNAL OF CELL BIOLOGY

Delivery of the aggregate inhibitor peptide QBP1 into the mouse brain using PTDs and its therapeutic effect on polyglutamine disease mice

(2008) H. Akiko Popiel et al.   NEUROSCIENCE LETTERS