Genome Editing and the Problem of Tetraploidy in Cell Modeling of the Genetic Form of Parkinsonism

Biochemistry (Mosc). 2018 Sep;83(9):1040-1045. doi: 10.1134/S0006297918090055.

Abstract

The prevalent form of familial parkinsonism is caused by mutations in the LRRK2 gene encoding for the mitochondrial protein kinase. In the review, we discuss possible causes of appearance of tetraploid cells in neuronal precursors obtained from induced pluripotent stem cells from patients with the LRRK2-associated form of parkinsonism after genome editing procedure. As LRRK2 protein participates in cell proliferation and maintenance of the nuclear envelope, spindle fibers, and cytoskeleton, mutations in the LRRK2 gene can affect protein functions and lead, via various mechanisms, to the mitotic machinery disintegration and chromosomal aberration. These abnormalities can appear at different stages of fibroblast reprogramming; therefore, editing of the LRRK2 nucleotide sequence should be done during or before the reprogramming stage.

Publication types

  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Gene Editing
  • Humans
  • Lamins / chemistry
  • Lamins / metabolism
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Microtubules / metabolism
  • Neurons / metabolism
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology*
  • Polymorphism, Single Nucleotide
  • Tetraploidy

Substances

  • Lamins
  • Ataxia Telangiectasia Mutated Proteins
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2