Huntington's Disease Related Research Tools

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.

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

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

GFAP

Laminin alpha 5/LAMA5

COL1

AAV8

GH1

GHRL

SORT1

AAV2 (N-term)

Norbin

AAV6

TLR9

Synaptogyrin 3

IL-6

CD45

USP9X

KCNMB2

β-actin

USP46

KCNIP3

ATRX

Peripherin

PIGR

NKRF

DCTN1

CD20

HPV(18) E2

GST tag

PLXNA3

CACNA1C

CD40

ACTA1

Chromogranin A

Related Products

Human Huntingtin (HTT) Assay Kit [CAT#: NRZP-1122-ZP52]

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