Induced pluripotent stem cells from Huntington's disease patients: a promising approach to define and correct disease-related alterations

• Published in: Neural regeneration research Vol. 14; no. 5; pp. 769 - 770
• Main Authors: Fatima, Azra, Gutiérrez-Garcia, Ricardo, Vilchez, David
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.05.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Institute for Genetics and Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Brain research; Consortia; Disease; DNA methylation; Epigenetics; Gene expression; Gene mutation; Genetic aspects; Huntington's disease; Huntingtons disease; Morphology; Mutation; Neurodegeneration; Proteins; Stem cells; Transcription factors
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.249223

[...]polyQ-expanded aggregates may collapse distinct proteostasis nodes such as protein clearance mechanisms (i.e., autophagy or the ubiquitin proteasome system) or the chaperone network (Koyuncu et al., 2017). [...]aberrant aggregates could sequester signalling and regulatory components such as transcription factors or physically obstruct neuronal extensions. Besides aggregates, growing evidence indicates that intermediate species called “oligomers” formed during the aggregation or disaggregation process also contribute to neurotoxicity. In these lines, downregulation of wild-type HTT levels induces HD-related changes such as progressive neurodegeneration and motor dysfunction or aggravate these changes in HD models. [...]overexpression of wild-type HTT improves brain cell survival and ameliorates the deleterious effects of the mutant protein (Saudou and Humbert, 2016). Given the strong link of HTT with neural development and the control of the epigenetics landscape, the study of pluripotent stem cells can shed light on the mechanisms underlying this process. Because epigenetic marks are reversible, research on HD-iPSCs can also lead to novel interventions to correct epigenetic and differentiation alterations at earlier developmental stages, which can contribute to disease phenotypes.