Neuron
Volume 7, Issue 2, August 1991, Pages 337-347
Journal home page for Neuron

Article
The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein

https://doi.org/10.1016/0896-6273(91)90272-2Get rights and content

Abstract

We have purified and characterized the growth inhibitory factor (GIF) that is abundant in the normal human brain, but greatly reduced in the Alzheimer's disease (AD) brain. GIF inhibited survival and neurite formation of cortical neurons in vitro. Purified GIF is a 68 amino acid small protein, and its amino acid sequence is 70% identical to that of human metallothionein II with a 1 amino acid insert and a unique 6 amino acid insert in the NH2— terminalandtheCOOH-terminalportions,respectively. The antibodies to the unique sequence of GIF revealed a distinct subset of astrocytes in the gray matter that appears to be closely associated with neuronal perikarya and dendrites. In the AD cortex, the number of GIF-positive astrocytes was drastically reduced, suggesting that GIF is down-regulated in the subset of astrocytes during AD.

References (78)

  • D.G. Higgins et al.

    CLUSTAL: a package for performing multiple sequence alignment on a microcomputer

    Gene

    (1988)
  • Y. Ihara

    Massive somatodendritic sprouting of cortical neurons in Alzheimer's disease

    Brain Res.

    (1988)
  • Y. Ihara

    What mediates between β-amyloid and paired helical filaments?

    Neurobiol. Aging

    (1989)
  • M. Karin

    Metallothioneins: proteins in search of function

    Cell

    (1985)
  • T. Kitamura et al.

    GFA-protein gene expression on the astroglia in cow and rat brains

    Brain Res.

    (1987)
  • J. Kondo et al.

    The carboxyl third of tau is tightly bound to paired helical filaments

    Neuron

    (1988)
  • D.M.A. Mann

    Cerebral amyloidosis, aging and Alzheimer's disease: a contribution from studies on Down's syndrome

    Neurobiol. Aging

    (1989)
  • C.Q. Mountjoy et al.

    Cortical neuronal counts in normal elderly controls and demented patients

    Neurobiol. Aging

    (1983)
  • M.M. Paula-Barbosa et al.

    Dendritic degeneration and regrowth in the cerebral cortex of patients with Alzheimer's disease

    J. Neurol. Sci.

    (1980)
  • A. Probst et al.

    Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region

    Brain Res.

    (1983)
  • A.B. Scheibel et al.

    Dendritic sprouting in Alzheimer's presenile dementia

    Exp. Neurol.

    (1978)
  • P. Schultze et al.

    Conformation of [Cd7]-metal loth ionein-2 from rat liver in aqueous solution determined by nuclear magnetic resonance spectroscopy

    J. Mol. Biol.

    (1988)
  • B.E. Tomlinson et al.

    Cell loss in the locus ceruleus in senile dementia of Alzheimer type

    J. Neurol. Sci.

    (1981)
  • Y. Uchida et al.

    Neurotrophic action of Alzheimer's disease brain extract is due to the loss of inhibitory factors for survival and neurite formation of cerebral cortical neurons

    Brain Res.

    (1989)
  • Y. Uchida et al.

    Alzheimer's disease brain extract stimulates the survival of cerebral cortical neurons from neonatal rats

    Biochem. Biophys. Res. Commun.

    (1988)
  • S.H. Appel

    A unifying hypothesis for the cause of amyotrophic lateral sclerosis, Parkinsonism, and Alzheimer's disease

    Ann. Neurol.

    (1981)
  • M.J. Ball

    Neuronal loss, neurofibrillary tangles and granulo-vacuolar degeneration in the hippocampus with aging and dementia. A quantitative study

    Acta Neuropathol.

    (1977)
  • W. Bondareff et al.

    Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus ceruleus) in senile dementia

    Neurology

    (1982)
  • H. Braak et al.

    Neuropil threads occur in dendrites of tangle-bearing nerve cells

    Neuropathol. Appl. Neurobiol.

    (1988)
  • J.P. Brion et al.

    Senile dementia of the Alzheimer type: morphological and immunocytochemical studies

  • B. Brugg et al.

    PC12 cells express juvenile microtubule-associated proteins during NGF-induced neurite outgrowth

    J. Cell Biol.

    (1988)
  • H. Crystal et al.

    Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease

    Neurology

    (1988)
  • K.G. Danielson et al.

    Immunochemical detection of metallothionein in specific epithelial cells of rat organs

  • L. Davies et al.

    A4 amyloid protein deposition and the diagnosis of Alzheimer's disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques

    Neurology

    (1988)
  • A. Delacourte

    General and dramatic glial reaction in Alzheimer brains

    Neurology

    (1990)
  • C.A. Dinarello

    Biology of interleukin 1

    FASEB J.

    (1988)
  • P.E. Duffy et al.

    Glial fibrillary acidic protein and Alzheimer-type senile dementia

    Neurology

    (1980)
  • J.R. Duguid et al.

    Changes in brain gene expression shared by scrapie and Alzheimer disease

  • M.A. Dunn et al.

    Metallothionein

  • Cited by (0)

    §

    Deceased.

    View full text