کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4326005 1614052 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of matrix metalloproteinase 2 by oligomeric amyloid β protein
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Regulation of matrix metalloproteinase 2 by oligomeric amyloid β protein
چکیده انگلیسی

Matrix metalloproteinases (MMPs) are a group of proteinases that degrade components of the extracellular matrix (ECM). There is increasing evidence for a link between the activation of MMPs and Alzheimer's disease (AD) pathogenesis, in which both beneficial and detrimental actions of MMPs have been suggested. It has been demonstrated that MMPs could degrade amyloid β (Aβ) and play important roles in the extracellular Aβ catabolism and clearance. On the other hand, MMPs could contribute to AD pathogenesis by compromising the blood brain barrier and promoting neurodegeneration. In the present study, we observed that oligomeric Aβ regulates MMP2 expression in a paradoxical manner. In rat primary astrocyte cultures, oligomeric Aβ down-regulated MMP2 transcription and reduced its extracellular activity. However, in a widely used mouse model for AD, immunohistochemistry demonstrated an increase of MMP2 expression in astrocytes surrounding senile plaques in APP/PS1 transgenic mice brains. Using real-time PCR, we found that the MMP2 mRNA level was elevated in APP/PS1 transgenic mice brains. In addition, elevated mRNA levels of MMP stimulating cytokines such as IL-1β and TGFβ were found in the brains of APP/PS1 mice. Our study suggests a complex regulation of MMP2 expression by oligomeric Aβ in astrocytes. While oligomeric Aβ directly down-regulates MMP2 expression and activation in astrocytes, it induces production of proinflammatory cytokines which could serve as strong stimulators for MMP2. Therefore, the ultimate outcome of the oligomeric Aβ on MMP2 activation in astrocytes might be the combination of its direct inhibitory action on astrocyte MMP2 expression and the secondary action of inducing inflammatory cytokines.

Research Highlights
► Oligomeric Aβ inhibits MMP2 activation in primary astrocyte cultures.
► Increase of MMP2 expression in astrocytes in APP/PS1 transgenic mice brains.
► Involvement of microglia and inflammatory cytokines in MMP2 activation in astrocyte.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1387, 28 April 2011, Pages 141–148
نویسندگان
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