期刊
NEUROTOXICITY RESEARCH
卷 17, 期 3, 页码 257-267出版社
SPRINGER
DOI: 10.1007/s12640-009-9098-x
关键词
Alzheimer's disease; Pro-nerve growth factor; p75 NTR; Neuron; Viability; Neurite growth; Amyloid-beta
资金
- NHMRC [480422]
- IPRS
Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-beta peptides (A beta), neurofibrillary tangles, distinctive neuronal loss and neurite dystrophy. Nerve growth factor (NGF) has been suggested to be involved in the pathogenesis of AD, however, the role of its precursor (proNGF) in AD remains unknown. In this study, we investigated the effect of proNGF on neuron death, neurite growth and A beta production, in vitro and in vivo. We found that proNGF promotes the death of different cell lines and primary neurons in culture, likely dependent on the expression of p75(NTR). We for the first time found that proNGF has an opposite role in neurite growth to that of mature NGF, retarding neurite growth in both cell lines and primary neurons. proNGF is localized to the A beta plaques in AD mice brain, however, it had no significant effect on A beta production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.
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