The Precursor Pro-Nerve Growth Factor Is the Predominant Form of Nerve Growth Factor in Brain and Is Increased in Alzheimer's Disease

@article{Fahnestock2001ThePP,
  title={The Precursor Pro-Nerve Growth Factor Is the Predominant Form of Nerve Growth Factor in Brain and Is Increased in Alzheimer's Disease},
  author={Margaret Fahnestock and Bernadeta Michalski and Bin Xu and Michael D. Coughlin},
  journal={Molecular and Cellular Neuroscience},
  year={2001},
  volume={18},
  pages={210-220}
}
Nerve growth factor (NGF) is important for regulation, differentiation, and survival of peripheral and central nervous system neurons, including basal forebrain cholinergic neurons (BFCN) which degenerate in Alzheimer's disease (AD). Mature NGF protein is processed from a larger precursor, proNGF. We demonstrate that proNGF is the predominant form of NGF in mouse, rat, and human brain tissue, whereas little or no mature NGF is detected. Previous reports showed NGF protein, measured by ELISA, is… 

Figures and Tables from this paper

Biological Activity of Nerve Growth Factor Precursor Is Dependent upon Relative Levels of Its Receptors*
TLDR
It is shown that proNGF is neurotrophic regardless of mutations or tags, and no matter how it is purified or in which system it is expressed, and it is concluded that the relative level of pro NGF receptors determines whether this precursor exhibits neurotrophic or apoptotic activity.
THE NERVE GROWTH FACTOR PRECURSOR PRONGF EXHIBITS NEUROTROPHIC ACTIVITY SIMILAR TO THAT OF MATURE NERVE GROWTH FACTOR
TLDR
Survival and neurite outgrowth assays on murine superior cervical ganglion neurons and PC12 cells indicated that proNGF exhibits neurotrophic activity similar to mature 2.5S NGF, but is approximately five-fold less active, suggesting that pro NGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo.
The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease.
Dysfunction of nerve growth factor (NGF) and its high (TrkA) and low (p75NTR) affinity receptors has been suggested to underlie the selective degeneration of the nucleus basalis (NB) cholinergic
Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade.
  • M. Bruno, A. Cuello
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2006
In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF)
Effects of proNGF on Neuronal Viability, Neurite Growth and Amyloid-beta Metabolism
TLDR
It is found that proNGF promotes the death of different cell lines and primary neurons in culture, likely dependent on the expression of p75NTR, and for the first time it has an opposite role in neurite growth to that of mature NGF, retarding neurites growth in both cell linesand primary neurons.
The nerve growth factor precursor proNGF exhibits neurotrophic activity but is less active than mature nerve growth factor
TLDR
Survival and neurite outgrowth assays on murine superior cervical ganglion neurons and PC12 cells indicated that proNGF exhibits neurotrophic activity similar to mature 2.5S NGF, but is approximately fivefold less active, suggesting that pro NGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo.
Amyloid &bgr;-Induced Nerve Growth Factor Dysmetabolism in Alzheimer Disease
TLDR
Evidence of diminished conversion of pro-NGF to its mature form and of greater NGF degradation in Alzheimer disease (AD) brain samples compared with controls is presented and alterations of the NGF metabolic pathway likely resulted in the increased pro- NGF levels.
...
...

References

SHOWING 1-10 OF 73 REFERENCES
Nerve Growth Factor and Alzheimer's Disease
TLDR
NGF and its low affinity receptor are abundantly present within the AD brain, although this does not rule out an NGF-related mechanism in the degeneration of basal forebrain neurons, nor does it eliminate the possibility that exogenous NGF may be successfully used to treat AD.
Nerve growth factor and Alzheimer's disease
TLDR
Findings in experimental animals indicate that nerve growth factor (NGF), a well‐characterized protein, acts as a neurotrophic factor for cholinergic neurons of the basal forebrain and suggest that increasing the availability of NGF to human cholineric cells might promote their survival in certain disease processes.
Differential Sorting of Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Hippocampal Neurons
Nerve growth factor (NGF) is released through the constitutive secretory pathway from cells in peripheral tissues and nerves where it can act as a target-derived survival factor. In contrast,
Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation.
TLDR
Results support the concept that NGF acts as trophic factor for magnocellular cholinergic neurons of the basal forebrain, and mRNANGF was found in the hippocampus and cortex but not in the septum.
Human beta-nerve growth factor gene sequence highly homologous to that of mouse.
TLDR
The isolation of mouse beta-NGF complementary DNA (cDNA) is described and its nucleotide sequence is presented, which predicts a prepro-beta-NGf molecule of Mr 27,000 (27K) and a pro-beta -NGF molecule ofMr 25K.
Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases.
TLDR
This comparative study shows that the three candidate mammalian subtilisin/kexin-like convertases identified process proNGF into NGF and that the nature of the final processed products is dependent on the intracellular environment.
Human β-nerve growth factor gene sequence highly homologous to that of mouse
TLDR
The isolation of mouse β-NGF complementary DNA (cDNA) is described and its nucleotide sequence is presented, which predicts a prepro-β- NGF molecule of Mr 27,000 (27K) and a pro-β -NGF molecules of Mr 25K.
...
...