The Effectiveness of Normalising Neurotrophic Signaling as Treatment Strategies for Huntington’s Disease

Authors

  • Zita Ng Student

DOI:

https://doi.org/10.47611/jsrhs.v11i4.3352

Keywords:

Huntington's Disease

Abstract

Huntington’s Disease (HD) is an inherited neurodegenerative disorder. It is established that BDNF deficiency and the imbalance of the p75NTR/TrkB expression are responsible for striatal atrophy in HD patients, which collectively provide a molecular explanation to the most significant hallmark symptom of HD - Chorea. Hence, normalising the neurotrophin receptor signalings can be and will be an effective treatment option due to the potential ameliorative effects that it may have on the neuropathological, and physiological conditions of the HD patients.

Downloads

Download data is not yet available.

References or Bibliography

Aethyta. (2016, January 9). LM22A-4 structure. https://commons.wikimedia.org/wiki/File:LM22A-4_structure.svg

Amitriptyline Hydrochloride. (n.d.). TCI . Retrieved November 28, 2021, from https://www.tcichemicals.com/HK/en/p/A0908

Arrasate, M., & Finkbeiner, S. (2012). Protein aggregates in Huntington’s disease. In Experimental Neurology (Vol. 238, Issue 1, pp. 1–11). https://doi.org/10.1016/j.expneurol.2011.12.013

Bai, Y., Xu, J., Brahimi, F., Zhuo, Y., Sarunic, M. v., & Uri Saragovi, H. (2010). An agonistic TrKb mAb causes sustained TrkB activation, delays RGC death, and protects the retinal structure in optic nerve axotomy and in glaucoma. Investigative Ophthalmology and Visual Science, 51(9), 4722–4731. https://doi.org/10.1167/iovs.09-5032

Baydyuk, M., & Xu, B. (2014). BDNF signaling and survival of striatal neurons. In Frontiers in Cellular Neuroscience (Vol. 8, Issue AUG). https://doi.org/10.3389/fncel.2014.00254

Benarroch, E. E. (2015). CLINICAL IMPLICATIONS OF NEUROSCIENCE RESEARCH Section Editor Brain-derived neurotrophic factor Regulation, effects, and potential clinical relevance.

Boyce, V. S., Park, J., Gage, F. H., & Mendell, L. M. (2012). Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats. European Journal of Neuroscience, 35(2), 221–232. https://doi.org/10.1111/j.1460-9568.2011.07950.x

Brito, V., Puigdellívol, M., Giralt, A., del Toro, D., Alberch, J., & Ginés, S. (2013). Imbalance of p75NTR/TrkB protein expression in Huntington’s disease: Implication for neuroprotective therapies. Cell Death and Disease, 4(4). https://doi.org/10.1038/cddis.2013.116

Chemgirl131. (2010, March 29). N-Acetylserotonin. https://commons.wikimedia.org/wiki/File:N-Acetylserotonin.png

Chen, C., Wang, Z., Zhang, Z., Liu, X., Kang, S. S., Zhang, Y., & Ye, K. (2018). The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 115(3), 578–583. https://doi.org/10.1073/pnas.1718683115

Dittrich, F., Gu¨, G., Ochs, G., Große-Wilde, A., Berweiler, U., Yan, Q., Miller, J. A., Toyka, K. v, & Sendtner, M. (1996). Pharmacokinetics of Intrathecally Applied BDNF and Effects on Spinal Motoneurons.

Garfield, E. (1987). Stanley Cohen’s and Rita Levi-kfontdcini’s Discoveries of Growth Factors Lead to 1986 Nobel in Medicine. 10, 106.

Ginés, S., Bosch, M., Marco, S., Gavaldà, N., Díaz-Hernández, M., Lucas, J. J., Canals, J. M., & Alberch, J. (2006). Reduced expression of the TrkB receptor in Huntington’s disease mouse models and in human brain. European Journal of Neuroscience, 23(3), 649–658. https://doi.org/10.1111/j.1460-9568.2006.04590.x

Ginés, S., Paoletti, P., & Alberch, J. (2010). Impaired TrkB-mediated ERK1/2 activation in huntington disease knock-in striatal cells involves reduced p52/p46 Shc expression. Journal of Biological Chemistry, 285(28), 21537–21548. https://doi.org/10.1074/jbc.M109.084202

Gong, Y., Cao, P., Yu, H. J., & Jiang, T. (2008). Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex. Nature, 454(7205), 789–793. https://doi.org/10.1038/nature07089

Greene, L. A., & Kaplan, D. R. (1995). Early events in neurotrophin signalling via Trk and p75 receptors. In Current Opinion in Neurobiology (Vol. 5).

Harraz, O. F., Hill-Eubanks, D., & Nelson, M. T. (2020). PIP2: A critical regulator of vascular ion channels hiding in plain sight. Proceedings of the National Academy of Sciences of the United States of America, 117(34), 20378–20389. https://doi.org/10.1073/pnas.2006737117

Ivanisevic, L., & Saragovi, H. U. (2013). Neurotrophins. In Handbook of Biologically Active Peptides (pp. 1639–1646). Elsevier Inc. https://doi.org/10.1016/B978-0-12-385095-9.00224-4

Jang, S. W., Liu, X., Chan, C. B., Weinshenker, D., Hall, R. A., Xiao, G., & Ye, K. (2009). Amitriptyline is a TrkA and TrkB Receptor Agonist that Promotes TrkA/TrkB Heterodimerization and Has Potent Neurotrophic Activity. Chemistry and Biology, 16(6), 644–656. https://doi.org/10.1016/j.chembiol.2009.05.010

Jang, S. W., Liu, X., Pradoldej, S., Tosini, G., Chang, Q., Iuvone, P. M., & Ye, K. (2010). N-acetylserotonin activates TrkB receptor in a circadian rhythm. Proceedings of the National Academy of Sciences of the United States of America, 107(8), 3876–3881. https://doi.org/10.1073/pnas.0912531107

Jang, S. W., Liu, X., Yepes, M., Shepherd, K. R., Miller, G. W., Liu, Y., Wilson, W. D., Xiao, G., Blanchi, B., Sun, Y. E., & Ye, K. (2010). A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proceedings of the National Academy of Sciences of the United States of America, 107(6), 2687–2692. https://doi.org/10.1073/pnas.0913572107

Jansen, P., Giehl, K., Nyengaard, J. R., Teng, K., Lioubinski, O., Sjoegaard, S. S., Breiderhoff, T., Gotthardt, M., Lin, F., Eilers, A., Petersen, C. M., Lewin, G. R., Hempstead, B. L., Willnow, T. E., & Nykjaer, A. (2007). Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury. Nature Neuroscience, 10(11), 1449–1457. https://doi.org/10.1038/nn2000

Jiao, S. S., Shen, L. L., Zhu, C., Bu, X. L., Liu, Y. H., Liu, C. H., Yao, X. Q., Zhang, L. L., Zhou, H. D., Walker, D. G., Tan, J., Götz, J., Zhou, X. F., & Wang, Y. J. (2016). Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Translational Psychiatry, 6(10). https://doi.org/10.1038/tp.2016.186

Knierim, J. (2020, October 20). Basal Ganglia. Neuroscience Online. https://nba.uth.tmc.edu/neuroscience/m/s3/chapter04.html

Knowles, J. K., Simmons, D. A., Nguyen, T. V. v., vander Griend, L., Xie, Y., Zhang, H., Yang, T., Pollak, J., Chang, T., Arancio, O., Buckwalter, M. S., Wyss-Coray, T., Massa, S. M., & Longo, F. M. (2013). A small molecule p75NTR ligand prevents cognitive deficits and neurite degeneration in an Alzheimer’s mouse model. Neurobiology of Aging, 34(8), 2052–2063. https://doi.org/10.1016/j.neurobiolaging.2013.02.015

Kowiański, P., Lietzau, G., Czuba, E., Waśkow, M., Steliga, A., & Moryś, J. (2018). BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. In Cellular and Molecular Neurobiology (Vol. 38, Issue 3, pp. 579–593). Springer New York LLC. https://doi.org/10.1007/s10571-017-0510-4

Li, E., & Hristova, K. (2006). Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. In Biochemistry (Vol. 45, Issue 20, pp. 6241–6251). https://doi.org/10.1021/bi060609y

Liu, C., Chan, C. B., & Ye, K. (2016). 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. In Translational Neurodegeneration (Vol. 5, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s40035-015-0048-7

Liu, X., Qi, Q., Xiao, G., Li, J., Luo, H. R., & Ye, K. (2013). O-methylated metabolite of 7,8-dihydroxyflavone activates TrkB receptor and displays antidepressant activity. Pharmacology, 91(3–4), 185–200. https://doi.org/10.1159/000346920

LM11A-31 dihydrochloride. (n.d.). Sigma-Aldrich. Retrieved November 28, 2021, from https://www.sigmaaldrich.com/HK/zh/product/sigma/sml0664

Longo, F. M., & Massa, S. M. (2013). Small-molecule modulation of neurotrophin receptors: A strategy for the treatment of neurological disease. In Nature Reviews Drug Discovery (Vol. 12, Issue 7, pp. 507–525). https://doi.org/10.1038/nrd4024

Mandel, A. L., Ozdener, H., & Utermohlen, V. (2011). Brain-derived neurotrophic factor in human saliva: Elisa optimization and biological correlates. Journal of Immunoassay and Immunochemistry, 32(1), 18–30. https://doi.org/10.1080/15321819.2011.538625

Marques Sousa, C., & Humbert, S. (2013). Huntingtin: Here, there, everywhere! Journal of Huntington’s Disease, 2(4), 395–403. https://doi.org/10.3233/JHD-130082

Massa, S. M., Xie, Y., Yang, T., Harrington, A. W., Mi, L. K., Sung, O. Y., Kraemer, R., Moore, L. A., Hempstead, B. L., & Longo, F. M. (2006). Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death. Journal of Neuroscience, 26(20), 5288–5300. https://doi.org/10.1523/JNEUROSCI.3547-05.2006

Massa, S. M., Yang, T., Xie, Y., Shi, J., Bilgen, M., Joyce, J. N., Nehama, D., Rajadas, J., & Longo, F. M. (2010). Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. Journal of Clinical Investigation, 120(5), 1774–1785. https://doi.org/10.1172/JCI41356

Mcfarland, K. N., & Cha, J. H. J. (2011). Molecular biology of Huntington’s disease. In Handbook of Clinical Neurology (Vol. 100). https://doi.org/10.1016/B978-0-444-52014-2.00003-3

Microswitch. (2007, January 1). Brain-derived neurotrophic factor. https://commons.wikimedia.org/wiki/File:Brain-derived_neurotrophic_factor_-_PDB_id_1BND.png

Ochs, G., Penn, R. D., York, M., Giess, R., Beck, M., Tonn, J., Haigh, J., Malta, E., Traub, M., Sendtner, M., & Toyka, K. v. (2000). A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 1(3), 201–206. https://doi.org/10.1080/14660820050515197

Pan, W., Banks, W. A., Fasold, M. B., Bluth, J., & Kastin, A. J. (1998). Transport of brain-derived neurotrophic factor across the blood-brain barrier. In Neuropharmacology (Vol. 37).

Rantamäki, T., Vesa, L., Antila, H., Lieto, A., Tammela, P., Schmitt, A., Lesch, K. P., Rios, M., & Castrén, E. (2011). Antidepressant drugs transactivate trkb neurotrophin receptors in the adult rodent brain independently of bdnf and monoamine transporter blockade. PLoS ONE, 6(6). https://doi.org/10.1371/journal.pone.0020567

Roos, R. A. C. (2010). Huntington’s disease: A clinical review. In Orphanet Journal of Rare Diseases (Vol. 5, Issue 1). https://doi.org/10.1186/1750-1172-5-40

Rubinsztein, D. C., Leggo, J., Coles, R., Almqvist, E., Biancalana, V., Cassiman, J.-J., Chotai, K., Connarty, M., Craufurd, D., Curtis, A., Curtis, D., Davidson, M. J., Differ, A.-M., Dode, C., Sherr, M., Abbott, M. H., Franz, M. L., Graham, C. A., Harper, P. S., … Hayden, M. R. (1996). Phenotypic Characterization of Individuals with 30-40 CAG Repeats in the Huntington Disease (HD) Gene Reveals HD Cases with 36 Repeats and Apparently Normal Elderly Individuals with 36-39 Repeats. In Am. J. Hum. Genet (Vol. 59).

Sahay, A. S., Sundrani, D. P., & Joshi, S. R. (2017). Neurotrophins: Role in Placental Growth and Development. Vitamins and Hormones, 104, 243–261. https://doi.org/10.1016/BS.VH.2016.11.002

Schlessinger, J. (2000). Cell Signaling by Receptor Review Tyrosine Kinases receptor) are monomers in the cell membrane. Ligand binding induces dimerization of these receptors re-sulting in autophosphorylation of their cytoplasmic do. In Cell (Vol. 103).

Shacham, T., Sharma, N., & Lederkremer, G. Z. (2019). Protein misfolding and ER stress in Huntington’s disease. In Frontiers in Molecular Biosciences (Vol. 6, Issue APR). Frontiers Media S.A. https://doi.org/10.3389/fmolb.2019.00020

Simmons, D. A. (2017). Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease. In Journal of Huntington’s Disease (Vol. 6, Issue 4, pp. 303–325). IOS Press. https://doi.org/10.3233/JHD-170275

Simmons, D. A., Belichenko, N. P., Yang, T., Condon, C., Monbureau, M., Shamloo, M., Jing, D., Massa, S. M., & Longo, F. M. (2013). A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2 and BACHD mouse models of huntington’s disease. Journal of Neuroscience, 33(48), 18712–18727. https://doi.org/10.1523/JNEUROSCI.1310-13.2013

Simmons, D. A., Mills, B. D., Butler, R. R., Kuan, J., McHugh, T. L. M., Akers, C., Zhou, J., Syriani, W., Grouban, M., Zeineh, M., & Longo, F. M. (2021). Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31. Neurotherapeutics, 18(2), 1039–1063. https://doi.org/10.1007/s13311-021-01023-8

Soderquist, R. G., Milligan, E. D., Sloane, E. M., Harrison, J. A., Douvas, K. K., Potter, J. M., Hughes, T. S., Chavez, R. A., Johnson, K., Watkins, L. R., & Mahoney, M. J. (2009). PEGylation of brain-derived neurotrophic factor for preserved biological activity and enhanced spinal cord distribution. Journal of Biomedical Materials Research - Part A, 91(3), 719–729. https://doi.org/10.1002/jbm.a.32254

Staats, P. S. (2008). Complications of intrathecal therapy. Pain Medicine, 9(SUPPL. 1). https://doi.org/10.1111/j.1526-4637.2008.00445.x

Study of LM11A-31-BHS in Mild-moderate AD Patients. (2017). U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT03069014

Tabrizi, S. J., Flower, M. D., Ross, C. A., & Wild, E. J. (2020). Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. In Nature Reviews Neurology (Vol. 16, Issue 10, pp. 529–546). Nature Research. https://doi.org/10.1038/s41582-020-0389-4

Tao, Y. S., Piao, S. G., Jin, Y. S., Jin, J. Z., Zheng, H. L., Zhao, H. Y., Lim, S. W., Yang, C. W., & Li, C. (2018). Expression of brain-derived neurotrophic factor in kidneys from normal and cyclosporine-treated rats. BMC Nephrology, 19(1). https://doi.org/10.1186/s12882-018-0852-2

Todd, D., Gowers, I., Dowler, S. J., Wall, M. D., McAllister, G., Fischer, D. F., Dijkstra, S., Fratantoni, S. A., van de Bospoort, R., Veenman-Koepke, J., Flynn, G., Arjomand, J., Dominguez, C., Munoz-Sanjuan, I., Wityak, J., & Bard, J. A. (2014). A monoclonal antibody TrkB receptor agonist as a potential therapeutic for huntington’s disease. PLoS ONE, 9(2). https://doi.org/10.1371/journal.pone.0087923

Zhang, X., Gureasko, J., Shen, K., Cole, P. A., & Kuriyan, J. (2006). An Allosteric Mechanism for Activation of the Kinase Domain of Epidermal Growth Factor Receptor. Cell, 125(6), 1137–1149. https://doi.org/10.1016/j.cell.2006.05.013

Zhao, X., Chen, X. Q., Han, E., Hu, Y., Paik, P., Ding, Z., Overman, J., Lau, A. L., Shahmoradian, S. H., Chiu, W., Thompson, L. M., Wu, C., & Mobley, W. C. (2016). TRiC subunits enhance BDNF axonal transport and rescue striatal atrophy in Huntington’s disease. Proceedings of the National Academy of Sciences of the United States of America, 113(38), E5655–E5664. https://doi.org/10.1073/pnas.1603020113

Zhou, H., Wang, J., Jiang, J., Stavrovskaya, I. G., Li, M., Li, W., Wu, Q., Zhang, X., Luo, C., Zhou, S., Sirianni, A. C., Sarkar, S., Kristal, B. S., Friedlander, R. M., & Wang, X. (2014). N-acetyl-serotonin offers neuroprotection through inhibiting mitochondrial death pathways and autophagic activation in experimental models of ischemic injury. Journal of Neuroscience, 34(8), 2967–2978. https://doi.org/10.1523/JNEUROSCI.1948-13.2014

Zuccato, C., & Cattaneo, E. (2007). Role of brain-derived neurotrophic factor in Huntington’s disease. In Progress in Neurobiology (Vol. 81, Issues 5–6, pp. 294–330). https://doi.org/10.1016/j.pneurobio.2007.01.003

Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B. R., Goffredo, D., Conti, L., MacDonald, M. E., Friedlander, R. M., Silani, V., Hayden, M. R., Timmusk, T., Sipione, S., & Cattaneo, E. (n.d.). Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease.

Zuccato, C., Marullo, M., Conforti, P., MacDonald, M. E., Tartari, M., & Cattaneo, E. (2008). Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington’s disease. Brain Pathology, 18(2), 225–238. https://doi.org/10.1111/j.1750-3639.2007.00111.x

Published

11-30-2022

How to Cite

Ng, Z. (2022). The Effectiveness of Normalising Neurotrophic Signaling as Treatment Strategies for Huntington’s Disease. Journal of Student Research, 11(4). https://doi.org/10.47611/jsrhs.v11i4.3352

Issue

Section

HS Research Projects