کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8626250 | 1568513 | 2018 | 28 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
NPCAMPsamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکinflammation - التهاب( توروم) Niemann-Pick disease type C - بیماری Niemann-Pick نوع CAlzheimer's disease - بیماری آلزایمرAlzheimer disease - بیماری آلزایمرALS - بیماری اسکلروز جانبی آمیوتروفیکShh - خیرSmoothened - صافsonic hedgehog - صدای جیر جیرAntimicrobial peptides - پپتیدهای پادمیکرب یا آنتیمایکروبیال پپتایدLearning and memory - یادگیری و حافظه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease](/preview/png/8626250.png)
چکیده انگلیسی
Emerging evidence suggests that neuro-inflammation begins early and drives the pathogenesis of Alzheimer's disease (AD), and anti-inflammatory therapies are under clinical development. However, several anti-inflammatory compounds failed to improve memory in clinical trials, indicating that reducing inflammation alone might not be enough. On the other hand, neuro-inflammation is implicated in a number of mental disorders which share the same therapeutic targets. Based on these observations, we screened a batch of genes related with mental disorder and neuro-inflammation in a classical olfactory conditioning in an amyloid beta (Aβ) overexpression fly model. A Smoothened (SMO) mutant was identified as a genetic modifier of Aβ toxicity in 3-min memory and downregulation of SMO rescued Aβ-induced 3-min and 1-h memory deficiency. Also, Aβ activated innate inflammatory response in fly by increasing the expression of antimicrobial peptides, which were alleviated by downregulating SMO. Furthermore, pharmaceutical administration of a SMO antagonist LDE rescued Aβ-induced upregulation of SMO in astrocytes of mouse hippocampus, improved memory in Morris water maze (MWM), and reduced expression of astrocyte secreting pro-inflammatory factors IL-1β, TNFα and the microglia marker IBA-1 in an APP/PS1 transgenic mouse model. Our study suggests that SMO is an important conserved modulator of Aβ toxicity in both fly and mouse models of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Genetics and Genomics - Volume 45, Issue 5, 20 May 2018, Pages 237-246
Journal: Journal of Genetics and Genomics - Volume 45, Issue 5, 20 May 2018, Pages 237-246
نویسندگان
Weiwei Ma, Mengnan Wu, Siyan Zhou, Ye Tao, Zuolei Xie, Yi Zhong,