Energy Metabolism and Mitochondrial Superoxide Anion Production in Pre-symptomatic Striatal Neurons Derived from Human-Induced Pluripotent Stem Cells Expressing Mutant Huntingtin
Sign Up to like & getrecommendations! Published in 2019 at "Molecular Neurobiology"
DOI: 10.1007/s12035-019-01734-2
Abstract: In the present study, we investigated whether mutant huntingtin (mHTT) impairs mitochondrial functions in human striatal neurons derived from induced pluripotent stem cells (iPSCs). Striatal neurons and astrocytes derived from iPSCs from unaffected individuals (Ctrl)… read more here.
Keywords: huntingtin; anion production; striatal neurons; superoxide anion ... See more keywords
Circadian Clocks Function in Concert with Heat Shock Organizing Protein to Modulate Mutant Huntingtin Aggregation and Toxicity
Sign Up to like & getrecommendations! Published in 2019 at "Cell reports"
DOI: 10.1016/j.celrep.2019.03.015
Abstract: SUMMARY Neurodegenerative diseases commonly involve the disruption of circadian rhythms. Studies indicate that mutant Huntingtin (mHtt), the cause of Huntington’s disease (HD), disrupts circadian rhythms often before motor symptoms are evident. Yet little is known… read more here.
Keywords: organizing protein; aggregation toxicity; heat shock; circadian clocks ... See more keywords
Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound.
Sign Up to like & getrecommendations! Published in 2019 at "Cell chemical biology"
DOI: 10.1016/j.chembiol.2019.07.001
Abstract: Aberrant activation of caspase-6 (C6) in the absence of other hallmarks of apoptosis has been demonstrated in cells and tissues from patients with Huntington disease (HD) and animal models. C6 activity correlates with disease progression… read more here.
Keywords: activation caspase; inhibitor; mutant huntingtin; activation ... See more keywords
Designing aptamers which respond to intracellular oxidative stress and inhibit aggregation of mutant huntingtin
Sign Up to like & getrecommendations! Published in 2018 at "Free Radical Biology and Medicine"
DOI: 10.1016/j.freeradbiomed.2018.03.052
Abstract: ABSTRACT Targeted expression of a therapeutic agent is a major bottleneck in designing a drug delivery system. Protein aggregation and elevated oxidative stress are associated with the onset of many neurodegenerative disorders, including Huntington's disease… read more here.
Keywords: aggregation; expression; mutant huntingtin; oxidative stress ... See more keywords
Lowering mutant huntingtin levels and toxicity: autophagy-endolysosome pathways in Huntington's disease.
Sign Up to like & getrecommendations! Published in 2019 at "Journal of molecular biology"
DOI: 10.1016/j.jmb.2019.11.012
Abstract: Huntington's disease is a monogenetic neurodegenerative disease, which serves as a model of neurodegeneration with protein aggregation. Autophagy has been suggested to possess a great value to tackle protein aggregation toxicity and neurodegenerative diseases. Current… read more here.
Keywords: huntington disease; disease; toxicity; mutant huntingtin ... See more keywords
Imaging Mutant Huntingtin Aggregates: Development of a Potential PET ligand.
Sign Up to like & getrecommendations! Published in 2020 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.0c00955
Abstract: Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of HD pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET)… read more here.
Keywords: pet; huntingtin aggregates; development; mutant huntingtin ... See more keywords
Design and Evaluation of [18F]CHDI-650 as a Positron Emission Tomography Ligand to Image Mutant Huntingtin Aggregates.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01585
Abstract: Therapeutic interventions are being developed for Huntington's disease (HD), a hallmark of which is mutant huntingtin protein (mHTT) aggregates. Following the advancement to human testing of two [11C]-PET ligands for aggregated mHTT, attributes for further… read more here.
Keywords: chdi 650; design evaluation; mutant huntingtin; ligand ... See more keywords
Polyglutamine-Specific Gold Nanoparticle Complex Alleviates Mutant Huntingtin-Induced Toxicity.
Sign Up to like & getrecommendations! Published in 2021 at "ACS applied materials & interfaces"
DOI: 10.1021/acsami.1c18754
Abstract: Huntington's disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we… read more here.
Keywords: toxicity; jld1; polyglutamine specific; mutant huntingtin ... See more keywords
Small-Molecule Disruptors of Mutant Huntingtin-Calmodulin Protein-Protein Interaction Attenuate Deleterious Effects of Mutant Huntingtin.
Sign Up to like & getrecommendations! Published in 2022 at "ACS chemical neuroscience"
DOI: 10.1021/acschemneuro.2c00305
Abstract: Huntington's disease is a progressive and lethal neurodegenerative disease caused by an increased CAG repeat mutation in exon 1 of the huntingtin gene (mutant huntingtin). Current drug treatments provide only limited symptomatic relief without impacting… read more here.
Keywords: huntington disease; huntingtin; mutant huntingtin; huntingtin calmodulin ... See more keywords
Conversion of a PROTAC Mutant Huntingtin Degrader into Small-Molecule Hydrophobic Tags Focusing on Drug-like Properties.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.1c00500.s002
Abstract: The onset of neurodegenerative disorders (NDs), such as Alzheimer's disease, is associated with the accumulation of aggregates of misfolded proteins. We previously showed that chemical knockdown of ND-related aggregation-prone proteins can be achieved by proteolysis… read more here.
Keywords: like properties; hydrophobic tags; drug like; mutant huntingtin ... See more keywords
Lowering mutant huntingtin protein
Sign Up to like & getrecommendations! Published in 2019 at "Nature Reviews Drug Discovery"
DOI: 10.1038/d41573-019-00207-4
Abstract: Human genetic studies have established the orphan G proteincoupled receptor gene, GPR146, as a regulator of plasma cholesterol levels. In line with these findings, Yu et al. report that depletion of GPR146 in mice substantially… read more here.
Keywords: huntingtin protein; mutant huntingtin; lowering mutant;