Increased production of beta-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2

Citation
N. Sato et al., Increased production of beta-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2, J BIOL CHEM, 276(3), 2001, pp. 2108-2114
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
3
Year of publication
2001
Pages
2108 - 2114
Database
ISI
SICI code
0021-9258(20010119)276:3<2108:IPOBAV>2.0.ZU;2-U
Abstract
An alternative spliced form of the presinilin 2 (PS2) gene (PS2V) lacking e xon 5 has previously been reported to be expressed in human brains in spora dic Alzheimer's disease (AD). PS2V encodes the amino-terminal portion of PS 2, which contains residues Met(1)-Leu(119) and 5 additional amino acid resi dues (SSMAG) at its carboxyl terminus. Here we report that PS2V protein imp aired the signaling pathway of the unfolded protein response, similarly to familial AD-linked PS1 mutants and caused significant increases in the prod uction of both amyloid beta (40) and beta (42). Interestingly, PS2V-encodin g protein was expressed in neuropathologically affected neurons of the hipp ocampal CA1 region and temporal cortex in AD patients. These findings sugge st that the aberrant splicing of the PS2 gene may be implicated in the neur opathology of sporadic AD.