UM
A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models
Song,Ju Xian1,2; Malampati,Sandeep2; Zeng,Yu1,2; Durairajan,Siva Sundara Kumar2,3; Yang,Chuan Bin2; Tong,Benjamin Chun Kit2; Iyaswamy,Ashok2; Shang,Wen Bin2,4; Sreenivasmurthy,Sravan Gopalkrishnashetty2; Zhu,Zhou2; Cheung,King Ho2; Lu,Jia Hong5; Tang,Chunzhi1; Xu,Nenggui1; Li,Min2
2020-02-01
Source PublicationAging Cell
ISSN1474-9718
Volume19Issue:2
AbstractAccumulating studies have suggested that targeting transcription factor EB (TFEB), an essential regulator of autophagy-lysosomal pathway (ALP), is promising for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, potent and specific small molecule TFEB activators are not available at present. Previously, we identified a novel TFEB activator named curcumin analog C1 which directly binds to and activates TFEB. In this study, we systematically investigated the efficacy of curcumin analog C1 in three AD animal models that represent beta-amyloid precursor protein (APP) pathology (5xFAD mice), tauopathy (P301S mice) and the APP/Tau combined pathology (3xTg-AD mice). We found that C1 efficiently activated TFEB, enhanced autophagy and lysosomal activity, and reduced APP, APP C-terminal fragments (CTF-β/α), β-amyloid peptides and Tau aggregates in these models accompanied by improved synaptic and cognitive function. Knockdown of TFEB and inhibition of lysosomal activity significantly inhibited the effects of C1 on APP and Tau degradation in vitro. In summary, curcumin analog C1 is a potent TFEB activator with promise for the prevention or treatment of AD.
KeywordAlzheimer's disease beta-amyloid curcumin analog C1 MAPT/Tau TFEB
DOI10.1111/acel.13069
URLView the original
Language英语
Fulltext Access
Citation statistics
Cited Times [WOS]:19   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorLi,Min
Affiliation1.Medical College of Acupuncture-Moxibustion and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou,China
2.Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong
3.Division of Mycobiology & Neurodegenerative Disease Research,Department of Microbiology,School of Life Sciences,Central University of Tamil Nadu,Tiruvarur,India
4.School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong
5.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao
Recommended Citation
GB/T 7714
Song,Ju Xian,Malampati,Sandeep,Zeng,Yu,et al. A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models[J]. Aging Cell,2020,19(2).
APA Song,Ju Xian.,Malampati,Sandeep.,Zeng,Yu.,Durairajan,Siva Sundara Kumar.,Yang,Chuan Bin.,...&Li,Min.(2020).A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models.Aging Cell,19(2).
MLA Song,Ju Xian,et al."A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models".Aging Cell 19.2(2020).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Song,Ju Xian]'s Articles
[Malampati,Sandeep]'s Articles
[Zeng,Yu]'s Articles
Baidu academic
Similar articles in Baidu academic
[Song,Ju Xian]'s Articles
[Malampati,Sandeep]'s Articles
[Zeng,Yu]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Song,Ju Xian]'s Articles
[Malampati,Sandeep]'s Articles
[Zeng,Yu]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.