دورية أكاديمية
أعرض في EDS

A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models.

التفاصيل البيبلوغرافية
العنوان: A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models.
المؤلفون: Song JX; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Malampati S; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Zeng Y; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Durairajan SSK; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.; Division of Mycobiology & Neurodegenerative Disease Research, Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India., Yang CB; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Tong BC; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Iyaswamy A; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Shang WB; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China., Sreenivasmurthy SG; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Zhu Z; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Cheung KH; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China., Lu JH; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China., Tang C; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China., Xu N; Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China., Li M; Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
المصدر: Aging cell [Aging Cell] 2020 Feb; Vol. 19 (2), pp. e13069. Date of Electronic Publication: 2019 Dec 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-
مواضيع طبية MeSH: Alzheimer Disease/*drug therapy , Amyloid beta-Protein Precursor/*metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*metabolism , Curcumin/*therapeutic use , tau Proteins/*metabolism, Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Cell Line, Tumor ; Chromosome Pairing/drug effects ; Cognitive Dysfunction/drug therapy ; Curcumin/pharmacology ; Disease Models, Animal ; Glycogen Synthase Kinase 3 beta/metabolism ; Lysosomes/drug effects ; Lysosomes/metabolism ; Maze Learning/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motor Activity/drug effects ; Neurons/drug effects ; Neurons/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering
مستخلص: 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.
(© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: Alzheimer's disease; MAPT/Tau; TFEB; beta-amyloid; curcumin analog C1
المشرفين على المادة: 0 (Amyloid beta-Peptides)
0 (Amyloid beta-Protein Precursor)
0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
0 (RNA, Small Interfering)
0 (Tcfeb protein, mouse)
0 (tau Proteins)
EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
EC 2.7.11.1 (Gsk3b protein, mouse)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
IT942ZTH98 (Curcumin)
تواريخ الأحداث: Date Created: 20191221 Date Completed: 20201120 Latest Revision: 20210110
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6996953
DOI: 10.1111/acel.13069
PMID: 31858697
قاعدة البيانات: MEDLINE
الوصف
تدمد:1474-9726
DOI:10.1111/acel.13069