Caspase cleavage of members of the amyloid precursor family of proteins

Veronica Galvan, Sylvia Chen, Daniel Lu, Anna Logvinova, Paul Goldsmith, Edward H. Koo, Dale E. Bredesen

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

The synapse loss and neuronal cell death characteristic of Alzheimer's disease (AD) are believed to result in large part from the neurotoxic effects of β-amyloid peptide (Aβ), a 40-42 amino acid peptide(s) derived proteolytically from β-amyloid precursor protein (APP). However, APP is also cleaved intracellularly to generate a second cytotoxic peptide, C31, and this cleavage event occurs in vivo as well as in vitro and preferentially in the brains of AD patients (Lu et al. 2000). Here we show that APPC31 is toxic to neurons in primary culture, and that like APP, the APP family members APLP1 and possibly APLP2 are cleaved by caspases at their C-termini. The carboxy-terminal peptide derived from caspase cleavage of APLP1 shows a degree of neurotoxicity comparable to APPC31. Our results suggest that even though APLP1 and APLP2 cannot generate Aβ, they may potentially contribute to the pathology of AD by generating peptide fragments whose toxicity is comparable to that of APPC31.

Original languageEnglish (US)
Pages (from-to)283-294
Number of pages12
JournalJournal of neurochemistry
Volume82
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cytotoxic peptides
  • Neurodegeneration
  • Neuronal cell death
  • Neurotoxicity
  • β-amyloid precursor protein (APP)

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Galvan, V., Chen, S., Lu, D., Logvinova, A., Goldsmith, P., Koo, E. H., & Bredesen, D. E. (2002). Caspase cleavage of members of the amyloid precursor family of proteins. Journal of neurochemistry, 82(2), 283-294. https://doi.org/10.1046/j.1471-4159.2002.00970.x