title: Identification of a novel amino-terminal fragment of amyloid precursor protein in mouse neuroblastoma Neuro2a cell.
abstract: The amyloid precursor protein (APP) can be catabolized mainly via either an amyloidogenic or non-amyloidogenic pathway, leading to the production of amyloid beta (Abeta) or the secreted form of APP (sAPP), respectively. Abeta is a major component of deposits found in Alzheimer's disease brains and plays an important role in the pathogenesis of this disease, whereas sAPP (though it might have some neurotropic function) has a largely unknown function and metabolism. In this study, a novel 11-kDa APP amino-terminal fragment from Neuro2a cells (but also present in primary cultured neurons, glias, and mouse cerebral cortex) was characterized using mass spectrometric and amino acid sequence analyzes. We could not detect the fragment extracellularly, and suggest that it was generated in a non-secretory, acidic degradation pathway. As this is a fragment of sAPP, it is possible that inhibition of this pathway increases amount of sAPP and results in neuroprotection.
authors.affiliation: Laboratory for Neurodegeneration Signal, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Hoshino
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Koji
authors.initials: K
authors.lastname: Takio
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments