Signaling pathways controlling neural stem cells slow progressive brain disease

Cold Spring Harb Symp Quant Biol. 2008;73:403-10. doi: 10.1101/sqb.2008.73.018. Epub 2008 Nov 6.

Abstract

The identification and characterization of multipotent neural precursors open the possibility of transplant therapies, but this approach is complicated by the widespread pathology of many degenerative diseases. Activation of endogenous precursors that support regenerative mechanisms is a possible alternative. We have previously shown that Notch ligands promote stem cell survival in vitro. Here, we show that there is an intimate interaction between insulin and Notch receptor signaling. Notch ligands also expand stem cell numbers in vivo with correlated benefits in brain ischemia. We now show that insulin promotes recovery of injured dopamine neurons in the adult brain. This response suggests that activating survival mechanisms in neural stem cells will promote recovery from progressive degenerative disease.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adult
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain Diseases / drug therapy
  • Brain Diseases / metabolism*
  • Brain Diseases / pathology
  • Cell Survival / drug effects
  • Dopamine / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidopamine / toxicity
  • Rabbits
  • Rats
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Stem Cells / pathology

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes3 protein, mouse
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Notch
  • delta protein
  • Oxidopamine
  • Dopamine