Modeling Huntington's disease with induced pluripotent stem cells

Mol Cell Neurosci. 2013 Sep;56:50-64. doi: 10.1016/j.mcn.2013.02.005. Epub 2013 Feb 28.

Abstract

Huntington's disease (HD) causes severe motor dysfunction, behavioral abnormalities, cognitive impairment and death. Investigations into its molecular pathology have primarily relied on murine tissues; however, the recent discovery of induced pluripotent stem cells (iPSCs) has opened new possibilities to model neurodegenerative disease using cells derived directly from patients, and therefore may provide a human-cell-based platform for unique insights into the pathogenesis of HD. Here, we will examine the practical implementation of iPSCs to study HD, such as approaches to differentiate embryonic stem cells (ESCs) or iPSCs into medium spiny neurons, the cell type most susceptible in HD. We will explore the HD-related phenotypes identified in iPSCs and ESCs and review how brain development and neurogenesis may actually be altered early, before the onset of HD symptoms, which could inform the search for drugs that delay disease onset. Finally, we will speculate on the exciting possibility that ESCs or iPSCs might be used as therapeutics to restore or replace dying neurons in HD brains.

Keywords: Huntington's disease; IPSC; Induced pluripotent stem cells; MSN; Neurodegenerative disease; Stem cell models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Disease Models, Animal*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Humans
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Mice / genetics*
  • Neurogenesis
  • Neurons / cytology
  • Neurons / metabolism

Substances

  • Biomarkers