期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 276, 期 3, 页码 2108-2114出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M006886200
关键词
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An alternative spliced form of the presinilin 2 (PS2) gene (PS2V) lacking exon 5 has previously been reported to be expressed in human brains in sporadic Alzheimer's disease (AD). PS2V encodes the amino-terminal portion of PS2, which contains residues Met(1)-Leu(119) and 5 additional amino acid residues (SSMAG) at its carboxyl terminus. Here we report that PS2V protein impaired the signaling pathway of the unfolded protein response, similarly to familial AD-linked PS1 mutants and caused significant increases in the production of both amyloid beta (40) and beta (42). Interestingly, PS2V-encoding protein was expressed in neuropathologically affected neurons of the hippocampal CA1 region and temporal cortex in AD patients. These findings suggest that the aberrant splicing of the PS2 gene may be implicated in the neuropathology of sporadic AD.
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