Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism.
Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-beta peptides (Abeta), 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 Abeta 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 Abeta plaques in AD mice brain, however, it had no significant effect on Abeta production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.
Wang
Yan-Jiang
YJ
Department of Human Physiology, Flinders University, Adelaide, SA, Australia.
Valadares
Deborah
D
Sun
Ying
Y
Wang
Xin
X
Zhong
Jin-Hua
JH
Liu
Xiao-Hong
XH
Majd
Shohreh
S
Chen
Li
L
Gao
Chang-Yue
CY
Chen
Si
S
Lim
Yoon
Y
Pollard
Anthony
A
Salegio
Ernest A
EA
Aguilar
Ernest
E
Gai
Wei-Ping
WP
Yang
Miao
M
Zhou
Xin-Fu
XF
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000633:toxicity*; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D053764:Presenilin-1 / Q000235:genetics; D011498:Protein Precursors / Q000633:toxicity*; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor
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