کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4343335 1615097 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Increased GADD34 in oligodendrocytes in Alzheimer’s disease
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Increased GADD34 in oligodendrocytes in Alzheimer’s disease
چکیده انگلیسی


• GADD34 was increased in neurons and oligodendrocytes in human AD brains.
• GADD34 was significantly increased in the early stage of APP transgenic mice.
• GADD34 and GST-π-immunopositive oligodendrocytes were co-localized in the AD.

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) and abnormally phosphorylated tau which contribute to endoplasmic reticulum (ER) stress. Previous studies demonstrated that Aβ and a truncated fragment of Aβ induced death of oligodendrocytes in vitro. In addition, a triple-transgenic AD mouse model exhibits significant region-specific alterations in myelination patterns at time points preceding the appearance of Aβ accumulation. The growth arrest and DNA damage protein (GADD) 34 is up-regulated in response to ER stress and regulates subunit of protein phosphatase 1 (PP1) complex that dephosphorylates eukaryotic translation initiator factor 2α (elF2α). Thus, GADD34 is known as an ER stress regulator or ER stress marker. In a recent study, GADD34 was induced in the spinal cord glial cells of an amyotrophic lateral sclerosis (ALS) mouse model. It is interesting that reduced GADD34 delayed the onset of ALS and prolonged the survival period in the mouse model. In this study, we have demonstrated that GADD34 was increased in neurons of human AD brains. Additionally, this finding was also observed in oligodendrocytes in human AD brains. Furthermore, we showed that the expression levels of GADD34 in neurons and oligodendrocytes were significantly increased in the early stage of AD in the mouse model. As oligodendrocytes were more affected in the early stages of AD in this experimental model, ER stress of Aβ oligomers may be more related to oligodendrocytes than to neurons. These results suggest that GADD34 could be a therapeutic target for preventing ER stress in neuronal cells in AD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 602, 18 August 2015, Pages 50–55
نویسندگان
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