A specific survival response in dopamine neurons at most risk in Parkinson's disease.
The specific expression of fibroblast growth factor 20 (FGF-20) in the adult substantia nigra and the association between FGF-20 mutations and Parkinson's disease provoked exploration of the function of this growth factor. We show by gain- and loss-of-function in vitro experiments that FGF-20 promotes survival and stimulates dopamine (DA) release in a calbindin-negative subset of cells that are preferentially lost in Parkinson's disease. FGF-20 selectively activates tyrosine hydroxylase in calbindin-negative neurons. In the adult substantia nigra, calbindin-negative neurons specifically express high levels of FGFR1 (FGF receptor 1). These data show that FGF signals to elevate DA levels and protect the specific midbrain neuron type at most risk in Parkinson's patients.
Murase
Sachiko
S
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
McKay
Ronald D
RD
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D012306:Risk; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C416003:FGF20 protein, human; D005346:Fibroblast Growth Factors; D004298:Dopamine