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Targeting neural precursors in the adult brain rescues injured dopamine neurons.

Authors
  • Androutsellis-Theotokis, Andreas
  • Rueger, Maria A
  • Park, Deric M
  • Mkhikian, Haik
  • Korb, Erica
  • Poser, Steve W
  • Walbridge, Stuart
  • Munasinghe, Jeeva
  • Koretsky, Alan P
  • Lonser, Russel R
  • McKay, Ronald D
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Aug 11, 2009
Volume
106
Issue
32
Pages
13570–13575
Identifiers
DOI: 10.1073/pnas.0905125106
PMID: 19628689
Source
Medline
License
Unknown

Abstract

In Parkinson's disease, multiple cell types in many brain regions are afflicted. As a consequence, a therapeutic strategy that activates a general neuroprotective response may be valuable. We have previously shown that Notch ligands support neural precursor cells in vitro and in vivo. Here we show that neural precursors express the angiopoietin receptor Tie2 and that injections of angiopoietin2 activate precursors in the adult brain. Signaling downstream of Tie2 and the Notch receptor regulate blood vessel formation. In the adult brain, angiopoietin2 and the Notch ligand Dll4 activate neural precursors with opposing effects on the density of blood vessels. A model of Parkinson's disease was used to show that angiopoietin2 and Dll4 rescue injured dopamine neurons with motor behavioral improvement. A combination of growth factors with little impact on the vasculature retains the ability to stimulate neural precursors and protect dopamine neurons. The cellular and pharmacological basis of the neuroprotective effects achieved by these single treatments merits further analysis.

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