亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations

锡尔图因 NAD+激酶 西妥因1 下调和上调 阿尔茨海默病 老化 细胞生物学 生物 转基因 化学 生物化学 疾病 医学 遗传学 内科学 基因
作者
David J. Bonda,Hyoung‐gon Lee,Antoni Camins,Mercè Pallàs,Gemma Casadesús,Mark A. Smith,Xiongwei Zhu
出处
期刊:Lancet Neurology [Elsevier]
卷期号:10 (3): 275-279 被引量:204
标识
DOI:10.1016/s1474-4422(11)70013-8
摘要

Background Advances in gerontology have yielded crucial insights into the molecular and biochemical aspects of the ageing process. The sirtuin pathway, which is most notable for its association with the anti-ageing effects of calorie restriction, has received particular attention, and pharmacological or transgenic upregulation of the sirtuin pathway has shown promising results in laboratory models of ageing. Alzheimer's disease is a neurodegenerative disease that is imposing an increasing burden on society, and is the leading cause of senile dementia worldwide. The lack of therapies for Alzheimer's disease provides a strong incentive for the development of an effective treatment strategy and, interestingly, research has uncovered a mechanism of action of the sirtuin pathway that might have therapeutic potential for Alzheimer's disease. Recent developments SIRT1, one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases, has recently been shown to attenuate amyloidogenic processing of amyloid-β protein precursor (APP) in cell culture studies in vitro and in transgenic mouse models of Alzheimer's disease. Mechanistically, SIRT1 increases α-secretase production and activity through activation of the α-secretase gene ADAM10. Because α-secretase is the enzyme responsible for the non-amyloidogenic cleavage of APP, upregulation of α-secretase shifts APP processing to reduce the pathological accumulation of the presumptive toxic Aβ species that results from β-secretase and γ-secretase activity. Interestingly, the spatial patterns of Aβ deposition in the brain might correlate with increased aerobic glycolysis in those regions. Because aerobic glycolysis depletes cellular levels of NAD+ (through a decreased NAD+/NADH ratio), it is possible that a corresponding downregulation of the NAD+-dependent sirtuin pathway contributes to the amyloidogenic processing of APP. Where next? The specific inhibition of Aβ generation by SIRT1 coupled with the potential link between aerobic glycolysis, NAD+ depletion, and amyloidogenesis through the sirtuin pathway has translational implications. On the one hand, the possible underlying role of the sirtuin pathway in Alzheimer's disease onset and development might increase our understanding of this devastating condition. On the other hand, therapeutic upregulation of SIRT1 might provide opportunities for the amelioration of Alzheimer's-disease-type neuropathology through inhibition of amyloidogenesis. Ultimately, further analysis into both aspects is necessary if any progress is to be made.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
研友_VZG7GZ应助aaaaa采纳,获得10
13秒前
31秒前
aaaaa发布了新的文献求助20
39秒前
vvan发布了新的文献求助10
1分钟前
樱桃猴子应助科研通管家采纳,获得10
1分钟前
樱桃猴子应助科研通管家采纳,获得10
1分钟前
1分钟前
micomico完成签到 ,获得积分10
1分钟前
魔幻的代珊应助LYL采纳,获得10
1分钟前
aaaaa完成签到,获得积分10
1分钟前
下次一定发布了新的文献求助10
2分钟前
2分钟前
丁宇卓完成签到 ,获得积分10
2分钟前
2分钟前
胡涛涛发布了新的文献求助10
2分钟前
传奇3应助harrywoo采纳,获得10
2分钟前
胡涛涛完成签到,获得积分20
2分钟前
3分钟前
我是老大应助胡涛涛采纳,获得10
3分钟前
曹原阁完成签到 ,获得积分10
3分钟前
3分钟前
3分钟前
天天好心覃完成签到 ,获得积分10
4分钟前
4分钟前
zqq完成签到,获得积分0
4分钟前
咸鱼卷完成签到 ,获得积分10
4分钟前
4分钟前
4分钟前
harrywoo发布了新的文献求助10
4分钟前
疯狂喵完成签到 ,获得积分10
5分钟前
5分钟前
roccc完成签到 ,获得积分10
5分钟前
5分钟前
5分钟前
lq完成签到,获得积分10
5分钟前
单薄归尘完成签到 ,获得积分10
5分钟前
bkagyin应助lq采纳,获得10
5分钟前
搞怪代桃完成签到 ,获得积分20
5分钟前
harrywoo完成签到,获得积分10
5分钟前
5分钟前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Pharmacogenomics: Applications to Patient Care, Third Edition 1000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Genera Insectorum: Mantodea, Fam. Mantidæ, Subfam. Hymenopodinæ (Classic Reprint) 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3085403
求助须知:如何正确求助?哪些是违规求助? 2738274
关于积分的说明 7548787
捐赠科研通 2387890
什么是DOI,文献DOI怎么找? 1266194
科研通“疑难数据库(出版商)”最低求助积分说明 613332
版权声明 598569