Journal
NEUROBIOLOGY OF AGING
Volume 28, Issue 8, Pages 1148-1162Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2006.05.036
Keywords
Alzheimer disease; Cerebrolysin (R); progenitor cells; neuronal differentiation; neurogenesis; neurotrophic factors; ciliary neurotrophic factor; glial-derived neurotrophic factor; insulin-like growth factor-1; insulin-like growth factor-2; basic fibroblast growth factor
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The denture gyrus of adult mammalian brain contains neural progenitor cells with self-renewal and multi-lineage potential. The lineage and maturation of the neural progenitors are determined by the composition and levels of the trophic factors in their microenvironment. In Alzheimer disease (AD) brain, especially the hippocampus, the level of basic fibroblast growth factor (FGF-2) is markedly elevated. Here we show that elevated FGF-2 enhances the division and nestin levels of cultured adult rat hippocampal progenitors but impairs neuronal lineage determination and maturation of these cells in culture. The trophic factors ciliary neurotrophic factor (CNTF), glial-derived neurotrophic factor (GDNF), and insulin-like growth factors-1 and -2 (IGF-1, IGF-2) as well as an Alzheimer peptidergic drug, Cerebrolysin (R) (CL), in which we found these neurotrophic activities, counteract the effect of FGF-2 in inducing neuronal lineage (early neurogenesis). Whereas CNTF is the most active of the neurotrophic factors studied in promoting neurogenesis, CL, probably because of a combined effect of these factors, induces similar changes but without inhibiting cell proliferation. These findings suggest that CNTF, GDNF, IGF-1, and IGF-2 are promising therapeutic targets for AD and other diseases in which neurogenesis is probably inhibited. (c) 2006 Elsevier Inc. All rights reserved.
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