کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6803122 | 1433522 | 2018 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Prostaglandin J2 promotes O-GlcNAcylation raising APP processing by α- and β-secretases: relevance to Alzheimer's disease
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Prostaglandin J2 promotes O-GlcNAcylation raising APP processing by α- and β-secretases: relevance to Alzheimer's disease Prostaglandin J2 promotes O-GlcNAcylation raising APP processing by α- and β-secretases: relevance to Alzheimer's disease](/preview/png/6803122.png)
چکیده انگلیسی
Regulation of the amyloid precursor protein (APP) processing by α- and β-secretases is of special interest to Alzheimer's disease (AD), as these proteases prevent or mediate amyloid beta formation, respectively. Neuroinflammation is also implicated in AD. Our data demonstrate that the endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length APP (FL-APP) processing by α- and β-secretases. The decrease in FL-APP was independent of proteasomal, lysosomal, calpain, caspase, and γ-secretase activities. Moreover, PGJ2-treatment promoted cleavage of secreted APP, specifically sAPPα and sAPPβ, generated by α and β-secretase, respectively. Notably, PGJ2-treatment induced caspase-dependent cleavage of sAPPβ. Mechanistically, PGJ2-treatment selectively diminished mature (O- and N-glycosylated) but not immature (N-glycosylated only) FL-APP. PGJ2-treatment also increased the overall levels of protein O-GlcNAcylation, which occurs within the nucleocytoplasmic compartment. It is known that APP undergoes O-GlcNAcylation and that the latter protects proteins from proteasomal degradation. Our results suggest that by increasing protein O-GlcNAcylation levels, PGJ2 renders mature APP less prone to proteasomal degradation, thus shunting APP toward processing by α- and β-secretases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 62, February 2018, Pages 130-145
Journal: Neurobiology of Aging - Volume 62, February 2018, Pages 130-145
نویسندگان
Teneka Jean-Louis, Patricia Rockwell, Maria E. Figueiredo-Pereira,