Identification of 5.8 kda c-terminal fragments of alzheimer amyloid p protein precursor generated in the lysosomal system

Xiaoyan Sun, Tomoko Tashiro, Shunsaku Hirai, Haruyasu Yamaguchi

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Elucidation of the normal metabolic pathways of amyloid β protein precursor (AβPP) is one of the important fields in the study of Alzheimer's disease. It has been suggested that the endosomal-lysosomal pathway may play a key role in the metabolism ofAβPP. We prepared different subcellular fractions from rat brain using a discontinuous sucrose density gradient method. The lysosome-enriched fraction was identified morphologically and biochemically. Various antibodies against the C-terminus ofAβPP were employed to detect specific fragments of AβPP in different subcellular fractions by western blot. The bands of APPP fragments with apparent molecular weight of 5.8 kDa, possibly containing the whole cytoplasmic domain of AβPP, were present specifically in the lysosome-enriched fraction. The 5.8 kDa fragments were increased and full-length APPP was decreased during incubation of the lysosome-enriched fraction in acidic buffer. The results provided direct evidence for the degradation of AβPP in the lysosomal system. Our data indicate that the digestion of AβPP into these small peptides might be important in the pathogenesis of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalAmyloid
Volume1
Issue number2
DOIs
StatePublished - 1994
Externally publishedYes

    Fingerprint

Keywords

  • Alzheimer's disease
  • Amyloid β protein
  • Amyloid β protein precursor
  • Lysosomal pathway
  • Subcellular fraction

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)
  • Pathology and Forensic Medicine

Cite this