Iwatsubo, Takeshi

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage.

A Y Hung; E H Koo; C Haass; D J Selkoe (Profiled Authors: Selkoe, Dennis J; Haass, Christian; Koo, Edward H)

Department of Neurology, Harvard Medical School, Boston, MA.
Proceedings of the National Academy of Sciences of the United States of America 1992;89(20):9439-43.

Despite increasing evidence for a pathogenetic role for the beta-amyloid precursor protein (beta APP) in Alzheimer disease, the physiological function of the protein remains unclear. The expression of the neural-specific isoform containing 695 amino acids, beta APP695, is consistent with a role for the protein in neuronal development. In this study, we analyzed the expression of beta APP during the retinoic acid-induced neuronal differentiation of P19 murine embryonal carcinoma cells. Northern blot and RNase protection analyses show a selective increase in beta APP695 expression, concomitant with the morphologic differentiation of P19-derived neurons. Moreover, the time course of increase observed for the beta APP695 mRNA is paralleled by other neuronal-specific transcripts. A similar increase in beta APP695 is observed at the protein level. Furthermore, we show that levels of beta APP695 protein progressively increase during the in vitro differentiation of primary hippocampal neurons. The finding that beta APP695 increases selectively and progressively during neuronal differentiation in two different cell culture systems suggests that this isoform has an important cellular function during this process in the brain. Unlike beta APP in most peripheral cell types, the increased levels of beta APP found in terminally differentiated neuronal cells are not processed in significant amounts by secretory cleavage. Thus, differentiation of neurons is accompanied by increased beta APP695 expression and membrane retention of the protein as intact, full-length molecules that could serve as potential substrates for amyloidogenesis.

3 Originating Grant

• 1.

  SELKOE, DENNIS J

  LEADERSHIP AND EXCELLENCE IN ALZHEIMERS DISEASE

  1 August 1988 - 31 July 1995

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 5,792,330

• 2.

  SELKOE, DENNIS J

  Aging in the Brain: The Role of the Fibrous Proteins

  1 September 1985 - 30 April 2012

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 6,982,031

• 3.

  SELKOE, DENNIS J

  Aging in the Brain: Role of the Fibrous Proteins

  1 September 1985 - 30 April 2017

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 2,223,247

Scientific Context

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