Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The epigenetic regulator Bmi1 controls proliferation in many organs. Reexpression of cell cycle proteins such as cyclin-dependent kinases (CDKs) is a hallmark of neuronal apoptosis in neurodegenerative diseases. Here we address the potential role of Bmi1 as a key regulator of cell cycle proteins during neuronal apoptosis. We show that several cell cycle proteins are expressed in different models of retinal degeneration and required in the Rd1 photoreceptor death process. Deleting E2f1, a downstream target of CDKs, provided temporary protection in Rd1 mice. Most importantly, genetic ablation of Bmi1 provided extensive photoreceptor survival and improvement of retinal function in Rd1 mice, mediated by a decrease in cell cycle markers and regulators independent of p16(Ink4a) and p19(Arf). These data reveal that Bmi1 controls the cell cycle-related death process, highlighting this pathway as a promising therapeutic target for neuroprotection in retinal dystrophies.

Detaljer

Författare
  • Dusan Zencak
  • Karine Schouwey
  • Danian Chen
  • Per Ekström
  • Ellen Tanger
  • Rod Bremner
  • Maarten van Lohuizen
  • Yvan Arsenijevic
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Oftalmologi

Nyckelord

Originalspråkengelska
Sidor (från-till)E593-E601
TidskriftProceedings of the National Academy of Sciences
Volym110
Utgivningsnummer7
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa