Program in Molecular Medicine
Amino Acids, Peptides, and Proteins | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Molecular Biology | Nervous System Diseases
The huntingtin (HTT) protein in its mutant form is the cause of the inherited neurodegenerative disorder, Huntington's disease. Beyond its effects in the central nervous system, disease-associated mutant HTT causes aberrant phenotypes in myeloid-lineage innate immune system cells, namely monocytes and macrophages. Whether the wild-type form of the protein, however, has a role in normal human macrophage function has not been determined. Here, the effects of lowering the expression of wild-type (wt)HTT on the function of primary monocyte-derived macrophages from healthy, non-disease human subjects were examined. This demonstrated a previously undescribed role for wtHTT in maintaining normal macrophage health and function. Lowered wtHTT expression was associated, for instance, with a diminished release of induced cytokines, elevated phagocytosis and increased vulnerability to cellular stress. These may well occur by mechanisms different to that associated with the mutant form of the protein, given an absence of any effect on the intracellular signalling pathway predominantly associated with macrophage dysfunction in Huntington's disease.
huntingtin (HTT) protein, Huntington's disease, macrophages
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Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
O'Regan GC, Farag SH, Ostroff GR, Tabrizi SJ, Andre R. Wild-type huntingtin regulates human macrophage function. Sci Rep. 2020 Oct 14;10(1):17269. doi: 10.1038/s41598-020-74042-8. PMID: 33057179; PMCID: PMC7560844. Link to article on publisher's site
O'Regan GC, Farag SH, Ostroff GR, Tabrizi SJ, Andre R. (2020). Wild-type huntingtin regulates human macrophage function. Open Access Publications by UMMS Authors. https://doi.org/10.1038/s41598-020-74042-8. Retrieved from https://escholarship.umassmed.edu/oapubs/4440
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This work is licensed under a Creative Commons Attribution 4.0 License.