Affiliated with RC | false |
Status | 已發表Published |
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![]() | |
2020-02-01 | |
Source Publication | Aging Cell
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ISSN | 1474-9718 |
Volume | 19Issue:2 |
Abstract | Accumulating 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. |
Keyword | Alzheimer's Disease Beta-amyloid Curcumin Analog C1 Mapt/tau Tfeb |
DOI | 10.1111/acel.13069 |
URL | View the original |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Cell Biology ; Geriatrics & Gerontology |
WOS Subject | Cell Biology ; Geriatrics & Gerontology |
WOS ID | WOS:000503743700001 |
Scopus ID | 2-s2.0-85076766729 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Institute of Chinese Medical Sciences |
Corresponding Author | Li,Min |
Affiliation | 1.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,Tong,Benjamin Chun Kit,Iyaswamy,Ashok,Shang,Wen Bin,Sreenivasmurthy,Sravan Gopalkrishnashetty,Zhu,Zhou,Cheung,King Ho,Lu,Jia Hong,Tang,Chunzhi,Xu,Nenggui,&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). |
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