کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5844021 | 1127499 | 2014 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Genetic mouse models of brain ageing and Alzheimer's disease
ترجمه فارسی عنوان
مدل های موش های ژنتیکی پیری مغز و بیماری آلزایمر
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کلمات کلیدی
SAMP8SOD1SOD2POLGCu/Zn-superoxide dismutase - Cu / Zn-سوپر اکسید دیسموتازMitochondrial DNA - DNA میتوکندریاDNA polymerase γ - DNA پلیمراز cROS - ROSneuronal loss - از دست دادن نورونAlzheimer's disease - بیماری آلزایمرmtDNA - دیانای میتوکندریاییLife span - طول عمرMn-Superoxide dismutase - منو سوپراکسید دیسموتازAmyloid plaque - پلاک آمیلوئیدCognitive ageing - پیری شناختیReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
چکیده انگلیسی
Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 142, Issue 2, May 2014, Pages 244-257
Journal: Pharmacology & Therapeutics - Volume 142, Issue 2, May 2014, Pages 244-257
نویسندگان
Andras Bilkei-Gorzo,