@article{ca62cd0a295c4b06adc115777f1deed6,
title = "A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models",
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.",
keywords = "Alzheimer's disease, beta-amyloid, curcumin analog C1, MAPT/Tau, TFEB",
author = "Song, {Ju Xian} and Sandeep Malampati and Yu Zeng and Durairajan, {S S Kumar} and Chuanbin Yang and Tong, {Chun Kit Benjamin} and Ashok Iyaswamy and Shang, {Wen Bin} and Sreenivasmurthy, {Sravan Gopalkrishnashetty} and Zhou Zhu and Cheung, {King Ho} and Lu, {Jia Hong} and Chunzhi Tang and Nenggui Xu and Min Li",
note = "Funding Information: This study was supported by the following grants: RGC/GRF/HKBU121006/18, RGC/GRF/HKBU121014/17, NSFC/81773926, NSFC/81703487, HMRF/ 15163481, HMRF14150811, HKBU/RC‐IRCs/17‐18/03, HKBU/RC‐IRMS /15‐16/04, FRGII/17‐18/021, FRGII/16‐17/018, and Basic research projects of Shenzhen Science and Technology Program (No.: JCYJ20180507184656626) to Min Li; NSFC/81873375 to Chunzhi Tang; Key Laboratory of Acupuncture and Moxibustion of Traditional Chinese Medicine in Guangdong (No.: 2012A061400017) and Innovation to strengthen school project of Guangdong provincial education department‐national major cultivation project (No.: 2014GKXM031) to Nenggui Xu. The authors would like to thank Dr. Martha Dahlen for her English editing of this manuscript. Funding Information: This study was supported by the following grants: RGC/GRF/HKBU121006/18, RGC/GRF/HKBU121014/17, NSFC/81773926, NSFC/81703487, HMRF/ 15163481, HMRF14150811, HKBU/RC-IRCs/17-18/03, HKBU/RC-IRMS /15-16/04, FRGII/17-18/021, FRGII/16-17/018, and Basic research projects of Shenzhen Science and Technology Program (No.: JCYJ20180507184656626) to Min Li; NSFC/81873375 to Chunzhi Tang; Key Laboratory of Acupuncture and Moxibustion of Traditional Chinese Medicine in Guangdong (No.: 2012A061400017) and Innovation to strengthen school project of Guangdong provincial education department-national major cultivation project (No.: 2014GKXM031) to Nenggui Xu. The authors would like to thank Dr. Martha Dahlen for her English editing of this manuscript.",
year = "2020",
month = feb,
doi = "10.1111/acel.13069",
language = "English",
volume = "19",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "2",
}