Signaling pathways controlling neural stem cells slow progressive brain disease.
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.
Androutsellis-Theotokis
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A
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rueger
M A
MA
Mkhikian
H
H
Korb
E
E
McKay
R D G
RD
D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D004298:Dopamine; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D051880:Receptors, Notch; D012097:Repressor Proteins; C411886:Hes3 protein, mouse; C064045:delta protein