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Huntington's Disease Related Research Tools

Huntington's Disease (HD)

Huntington's disease (HD) is a lethal autosomal dominant and progressive neurodegenerative disorder, that is characterized by motor, cognitive, and behavioral impairment. At present, there are no disease-modifying treatments available other than some approaches to address certain specific symptoms of HD. HD is caused by a tandem repeat expansion mutation so that the trinucleotide (CAG) is expanded to become (CAG)n+x in the huntingtin (HTT) gene. This tandem repeat tract is transcribed and translated to become a (Q)n+x polyglutamine tract in the HTT protein. This mutant protein (mutHTT) leads to a cascade of molecular, cellular and systems changes, which, together with the modulatory actions of genetic and environmental modifiers, ultimately lead to the onset of disease symptoms.

Address mutHTT Modification and Degradation

Post-translational modifications (PTMs) of the HTT protein play an important role in the pathogenesis of HD. HTT is likely modified by SUMOylation, phosphorylation, palmitoylation, acetylation and these PTMs are important in proper protein-protein interactions of HTT. Histone acetyltransferase (HAT) enzymes CBP and PCAF were found to be inactivated by mutHTT through protein-protein interactions, leading to transcriptional and chromatin remodeling deregulation and contributing to the pathogenesis of HD. Thus, PTMs of HTT be exploited for therapeutic purposes to enhance the clearance of mutHTT. Besides, certain inhibitors of histone deacetylases (HDAC), deacetylase enzymes and mTOR have been shown to address mutHTT modification and degradation.

Address Signaling Pathways

One important HD pathology-associated change is in the cyclic AMP (cAMP) signaling and aberrant transcription of genes regulated by the cAMP response element (CRE). Inhibition of phosphodiesterase (PDE) 10A is shown to be beneficial against HD via restoration of CRE-mediated gene expression. Another important signaling pathway that contributes to the pathology of HD is MAPK signaling.

Potential pathological molecular events in HD and possible therapeutic interventions. Fig.1 Potential pathological molecular events in HD and possible therapeutic interventions. (Huang, 2016)

Decrease mutHTT Content

Reducing the content of mutHTT by inhibiting gene transcription, mRNA translation or promoting the breakdown of mRNA coding for HTT, may reduce any associated downstream damaging effects of mutHTT.

By using more sophisticated approaches incorporating modelling, computational biology and systems neuroscience, Creative Biolabs can obtain a more comprehensive and integrated understanding of the pathogenesis of HD, which will have major implications for therapeutic approaches aimed at preventing, treating and ultimately curing this devastating disease. Creative Biolabs offers comprehensive products for you. Products range from neural cell lines, medium, cell dyes to customized neural antibodies, peptides, recombinant proteins and assay kits.

Targets Related to HD

Process Strategy Popular Targets
Address mutHTT Modification and Degradation HDAC Inhibitor
Deacetylase Enzymes Inhibitors
mOTR Inhibitor
HDAC
Deacetylase Enzymes
mOTR
Address Signaling Pathways PDE10A Inhibitor; MKP-1 inhibitor; MLK-2 Inhibitor;
Kynurenine Monooxygenase (KMO) Inhibitors;
Extracellular Signal-regulated Kinase (ERK) Activator;
Transcription Factors Activator; cmGluR5 Antagonist
PDE 10A; MKP-1; MLK-2; KMO; ERK1/ERK 2; CREB; Elk-1; GPCR; mGluR5; PGC-1α
Decrease mutHTT Content Transcription by zinc finger proteins (ZFPs) Inhibitors
mutHTT Targeting Antisense Oligonucleotides (ASOs)
ZFP; mutHTT mRNA; mutHTT Protein

Reference

  1. Huang, W. J.; et al. Huntington's disease: Molecular basis of pathology and status of current therapeutic approaches. Experimental and therapeutic medicine. 2016, 12(4): 1951-1956.
Huntington's Disease Assay Service
For Research Use Only. Not For Clinical Use.

Target

Related Products
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Target: VWF

Amyotrophic Lateral Sclerosis,
Parkinson's, Alzheimer's and Huntington's diseases

Host Species:
Mouse
Species Reactivity:
Human
Applications:
IHC; WB
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