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

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Abstract

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 increased in AD BFCN target regions such as hippocampus and cortex. Using Western blotting, we demonstrate a twofold increase in proNGF in AD parietal cortex compared to controls, indicating that it is this precursor form, proNGF, that accumulates in AD. This increase may reflect either a role for biologically active proNGF or posttranslational disturbances in NGF biosynthesis that decrease the processing of proNGF to mature NGF in AD.

References (61)

  • C.F. Ibanez et al.

    Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product

    Cell

    (1992)
  • N. Jetté et al.

    NGF mRNA is not decreased in frontal cortex from Alzheimer's disease patients

    Mol. Brain Res.

    (1994)
  • D.R. Kaplan et al.

    Signal transduction by the neurotrophin receptors

    Curr. Opin. Cell Biol.

    (1997)
  • M. Kojima et al.

    Nerve growth factor induces trkA mRNA expression in cultured basal forebrain chrolinergic neurons from 17-day fetal rats

    Neurosci. Lett.

    (1994)
  • J. Lakshmanan et al.

    Molecular forms of nerve growth factor in mouse submaxillary glands

    Biochem. Biophys. Res. Commun.

    (1988)
  • E.J. Mufson et al.

    Reduction in p140-trkA receptor protein within the nucleus basalis and cortex in Alzheimer's disease

    Exp. Neurol.

    (1997)
  • A. Nitta et al.

    Memory impairment and neural dysfunction after continuous infusion of anti-nerve growth factor antibody into the septum in adult rats

    Neuroscience

    (1993)
  • M.R. Roberson et al.

    Cholinergic activity and amyloid precursor protein metabolism

    Brain Res. Rev.

    (1997)
  • R.J. Rylett et al.

    Role of neurotrophins in cholinergic-neurone function in the adult and aged CNS

    Trends Neurosci.

    (1994)
  • A. Salehi et al.

    Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease

    Neuroscience

    (1996)
  • M.C. Senut et al.

    Neuronal localization of the nerve growth factor precursor-like immunoreactivity in the rat brain

    Int. J. Dev. Neurosci.

    (1990)
  • S.H. Appel

    A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease

    Ann. Neurol.

    (1981)
  • E.A. Berger et al.

    Evidence for pro-beta-nerve growth factor, a biosynthetic precursor to beta-nerve growth factor

    Proc. Natl. Acad. Sci. USA

    (1977)
  • P.A. Bresnahan et al.

    Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-β-NGF in vivo

    J. Cell Biol.

    (1990)
  • K.S. Chen et al.

    Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits

    J. Neurosci.

    (1997)
  • J.T. Coyle et al.

    Alzheimer's disease: A disorder of cortical cholinergic innervation

    Science

    (1983)
  • K.A. Crutcher et al.

    Detection of NGF-like activity in human brain tissue: Increased levels in Alzheimer's disease

    J. Neurosci.

    (1993)
  • T.L.J. Darling et al.

    The biosynthesis and processing of proteins in the mouse 7S nerve growth factor complex

    Cold Spring Harb. Symp. Quant. Biol.

    (1983)
  • R. Delsite et al.

    Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth

    Prostate

    (1999)
  • E. Dicou et al.

    Synthesis of nerve growth factor mRNA and precursor protein in the thyroid and parathyroid glands of the rat

    Proc. Natl. Acad. Sci. USA

    (1986)

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