Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism

Y-J Wang; Deborah Valadares; Annie Sun; X Wang; Jin Hua Zhong; Xiaohong Liu; Li Cheng; Shohreh Majd; Chang Gao; Si Chen; Yoon Lim; Anthony Pollard; Ernest Aguilar; Weiping Gai; Miao Yang; Xin-Fu Zhou

doi:10.1007/s12640-009-9098-x

Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism

Y-J Wang, Deborah Valadares, Annie Sun, X Wang, Jin Hua Zhong, Xiaohong Liu, Li Cheng, Shohreh Majd, Chang Gao, Si Chen, Yoon Lim, Anthony Pollard, Ernest Aguilar, Weiping Gai, Miao Yang, Xin-Fu Zhou

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35 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-β peptides (Aβ), 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 Aβ 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 Aβ plaques in AD mice brain, however, it had no significant effect on Aβ production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.

Original language	English
Pages (from-to)	257-267
Number of pages	11
Journal	Neurotoxicity Research
Volume	17
Issue number	3
DOIs	https://doi.org/10.1007/s12640-009-9098-x
Publication status	Published - Apr 2010

Keywords

Alzheimer's disease
Amyloid-beta
Neurite growth
Neuron
Pro-nerve growth factor
Viability

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10.1007/s12640-009-9098-x

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title = "Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism",

abstract = "Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-β peptides (Aβ), 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 Aβ 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 Aβ plaques in AD mice brain, however, it had no significant effect on Aβ production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.",

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author = "Y-J Wang and Deborah Valadares and Annie Sun and X Wang and Zhong, {Jin Hua} and Xiaohong Liu and Li Cheng and Shohreh Majd and Chang Gao and Si Chen and Yoon Lim and Anthony Pollard and Ernest Aguilar and Weiping Gai and Miao Yang and Xin-Fu Zhou",

year = "2010",

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doi = "10.1007/s12640-009-9098-x",

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AU - Wang, Y-J

AU - Valadares, Deborah

AU - Sun, Annie

AU - Wang, X

AU - Zhong, Jin Hua

AU - Liu, Xiaohong

AU - Cheng, Li

AU - Majd, Shohreh

AU - Gao, Chang

AU - Chen, Si

AU - Lim, Yoon

AU - Pollard, Anthony

AU - Aguilar, Ernest

AU - Gai, Weiping

AU - Yang, Miao

AU - Zhou, Xin-Fu

PY - 2010/4

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N2 - Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-β peptides (Aβ), 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 Aβ 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 Aβ plaques in AD mice brain, however, it had no significant effect on Aβ production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.

AB - Alzheimer's disease (AD) is characterized pathologically by the deposition of amyloid-β peptides (Aβ), 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 Aβ 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 Aβ plaques in AD mice brain, however, it had no significant effect on Aβ production in vitro and in vivo. Our findings suggest that proNGF is an important factor involving AD pathogenesis.

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KW - Amyloid-beta

KW - Neurite growth

KW - Neuron

KW - Pro-nerve growth factor

KW - Viability

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DO - 10.1007/s12640-009-9098-x

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Effects of proNGF on neuronal viability, neurite growth and amyloid-beta metabolism

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Keywords

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