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.
Target
- Host Species:
- Mouse
- Species Reactivity:
- Mouse; Rat; Human
- Applications:
- WB; IP; IF; ELISA
- Conjugation:
- Unconjugated; APC; PE; HRP; Biotin; FITC; Alexa Fluor 488; Alexa Fluor 700; Alexa Fluor 647; Alexa Fluor 750; Alexa Fluor 594; Alexa Fluor 350; Alexa Fluor 2460
- NeuroMab™ Anti-Alpha Synuclein BBB Shuttle Antibody(NRZP-1022-ZP4050) (Cat#: NRZP-1022-ZP4050)
- NeuroMab™ Mouse Anti-EFNB2 Monoclonal Antibody (CBP1159) (Cat#: NAB-0720-Z4396)
- NeuroMab™ Anti-CD32b Antibody(NRP-0422-P1803) (Cat#: NRP-0422-P1803)
- NeuroMab™ Anti-ApoC3 BBB Shuttle Antibody(NRZP-1022-ZP3505) (Cat#: NRZP-1022-ZP3505)
- NeuroMab™ Anti-pTau Antibody(NRP-0422-P1719) (Cat#: NRP-0422-P1719)
- NeuroMab™ Anti-GARP Antibody(NRP-0422-P1639) (Cat#: NRP-0422-P1639)
- NeuroMab™ Anti-SEZ6 Antibody(NRP-0422-P517) (Cat#: NRP-0422-P517)
- NeuroMab™ Anti-CD20 Antibody(NRP-0422-P1230) (Cat#: NRP-0422-P1230)
- NeuroMab™ Anti-Tau Antibody(NRP-0422-P2275) (Cat#: NRP-0422-P2275)
- NeuroMab™ Anti-Tau Antibody(NRP-0422-P2293) (Cat#: NRP-0422-P2293)
- Green Fluorescent Tau SH-SY5Y cell Line (Cat#: NCL2110P219)
- Mouse Retinal Ganglion Cells (Cat#: NCL2110P145)
- iNeu™ Human Oligodendrocyte Progenitor Cells (OPCs) (Cat#: NCL-2103-P49)
- Human CMEC/D3 Cell Line, Blood-Brain Barrier Model (Cat#: NCL-2108-P020)
- iNeu™ Human Midbrain Dopaminergic Neurons (Cat#: NCL-21P6-003)
- Human Neurons Isolated from Cortex (Cat#: NCL-21P6-023)
- Mouse Glioma Cell Line GL261-GFP (Cat#: NCL-2108P04)
- Human Astrocytes, Immortalized (Cat#: NCL-2105-P182-AM)
- Green Fluorescent Alpha-synuclein SH-SY5Y Cell Line (Cat#: NCL2110P209)
- Rat Schwann Cells RSC96, Immortalized (Cat#: NCL-2108P21)
- Human GFAP ELISA Kit [Colorimetric] (Cat#: NPP2011ZP383)
- Human Poly ADP ribose polymerase,PARP Assay Kit (Cat#: NRZP-1122-ZP62)
- Human Tau Aggregation Kit (Cat#: NRP-0322-P2173)
- Beta Amyloid (1-42), Aggregation Kit (Cat#: NRZP-0323-ZP200)
- Alpha Synuclein Aggregation Kit (Cat#: NRZP-1122-ZP15)
- Alpha-Synuclein Aggregation Assay Kit (Cat#: NRZP-1122-ZP37)
- Amyloid beta 1-42 Kit (Cat#: NRP-0322-P2170)
- Beta Amyloid (1-40), Aggregation Kit, TTF Assay (Cat#: NRZP-0323-ZP199)
- pAAV-syn-FLEX-jGCaMP8s-WPRE (Cat#: NTA-2106-P066)
- Dextran-CYanine5.5 (Cat#: NTA-2011-ZP118)
- pAAV-EF1a-DIO-EGFP-WPRE (Cat#: NTA-2012AD-P285)
- AAV2/9-hEF1a-fDIO-eNpHR 3.0-mCherry-WPRE-pA (Cat#: NTA-2012-ZP78)
- AAV-EF1a-mCherry-flex-dtA (Cat#: NRZP-0622-ZP616)
- pAAV-hSyn-DIO-XCaMP-R-WPRE (Cat#: NTA-2012AD-P508)
- AAV2/2Retro-CAG-DIO-EGFP-2A-TetTox-pA [Neural Tracing] (Cat#: NTA-2012-ZP303)
- VSV-eGFP (Cat#: NTA-2011-ZP20)
- AAV-mDLX-CRE-tdTomato (Cat#: NRZP-0622-ZP721)
- AAV2/9-hEF1a-DIO-mCherry-P2A-TetTox-WPRE-pA (Cat#: NTA-2012-ZP268)
- ABCA1 Antisense Oligonucleotide (NV-2106-P27) (Cat#: NV-2106-P27)
- Human apolipoprotein E (APOE) (NM_000041) ORF clone, Untagged (Cat#: NEP-0421-R0232)
- Tau Antisense Oligonucleotide (IONIS-MAPTRx) (Cat#: NV-2106-P29)
- Lenti of Mouse synuclein, alpha (Snca) transcript variant (NM_001042451) ORF clone, mGFP Tagged (Cat#: NEP-0521-R0864)
- Human superoxide dismutase 3, extracellular (SOD3) (NM_003102) ORF clone, Untagged (Cat#: NEP-0521-R0808)
- App Rat amyloid beta (A4) precursor protein (App)(NM_019288) ORF clone, Untagged (Cat#: NEP-0421-R0053)
- Rat Parkinson disease (autosomal recessive, juvenile) 2, parkin (Park2) (NM_020093) ORF clone/lentiviral particle, Myc-DDK Tagged (Cat#: NEP-0621-R0041)
- Human superoxide dismutase 1, soluble (SOD1) (NM_000454) ORF clone, TurboGFP Tagged (Cat#: NEP-0521-R0748)
- Human presenilin 1 (PSEN1), transcript variant 2 (NM_007318) ORF clone, TurboGFP Tagged (Cat#: NEP-0421-R0140)
- Human huntingtin-associated protein 1 (HAP1) transcript variant 2 (NM_177977) ORF clone, Myc-DDK Tagged (Cat#: NEP-0521-R0676)
- NeuroBiologics™ Monkey Cerebrospinal Fluid (Cat#: NRZP-0822-ZP495)
- NeuroBiologics™ Rat Cerebrospinal Fluid (Cat#: NRZP-0822-ZP496)
- NeuroBiologics™ Mouse Cerebrospinal Fluid (Cat#: NRZP-0822-ZP497)
- NeuroBiologics™ Pig Cerebrospinal Fluid (Cat#: NRZP-0822-ZP498)
- NeuroBiologics™ Human Cerebrospinal Fluid (Cat#: NRZP-0822-ZP491)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP501)
- NeuroPro™ Anti-ASA BBB Shuttle Protein (Cat#: NRZP-0423-ZP504)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP500)
- NeuroPro™ Anti-EPO BBB Shuttle Protein (Cat#: NRZP-0423-ZP508)
- NeuroPro™ Anti-idursulfase BBB Shuttle Protein (Cat#: NRZP-0423-ZP497)
- NeuroPro™ Anti-NAGLU BBB Shuttle Protein (Cat#: NRZP-0423-ZP506)
- NeuroPro™ Anti-IDS BBB Shuttle Protein (Cat#: NRZP-0423-ZP503)
- NeuroPro™ Anti-SGSH BBB Shuttle Protein (Cat#: NRZP-0423-ZP505)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP510)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP509)