UM  > Institute of Chinese Medical Sciences
Affiliated with RCfalse
Status已發表Published
Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models
Iyaswamy, Ashok1,2; Wang, Xueli3; Krishnamoorthi, Senthilkumar1,4; Kaliamoorthy, Venkatapathy1; Sreenivasmurthy, Sravan G.1,2; Kumar Durairajan, Siva Sundara5; Song, Ju Xian1,6; Tong, Benjamin Chun kit1,2; Zhu, Zhou1,2; Su, Cheng Fu1,2; Liu, Jia1,2; Cheung, King Ho1,2; Lu, Jia Hong7; Tan, Jie Qiong8; Li, Hung Wing9; Wong, Man Shing3; Li, Min1,2
2022-05
Source PublicationRedox Biology
ISSN2213-2317
Volume51
Abstract

Accumulation of amyloid-β (Aβ) oligomers and phosphorylated Tau aggregates are crucial pathological events or factors that cause progressive neuronal loss, and cognitive impairments in Alzheimer's disease (AD). Current medications for AD have failed to halt, much less reverse this neurodegenerative disorder; therefore, there is an urgent need for the development of effective and safe drugs for AD therapy. In the present study, the in vivo therapeutic efficacy of an Aβ-oligomer-targeted fluorescent probe, F-SLOH, was extensively investigated in 5XFAD and 3XTg-AD mouse models. We have shown that F-SLOH exhibits an efficient inhibitory activity against Aβ aggregation in vivo, and acts as an effective theranostic agent for the treatment of multiple neuropathological changes in AD mouse models. F-SLOH has been found to significantly reduce not only the levels of Aβ oligomers, Tau aggregates and plaques but also the levels of amyloid precursor protein (APP) and its metabolites via autophagy lysosomal degradation pathway (ALP) in the brains of 5XFAD and 3XTg-AD mice. It also reduces astrocyte activation and microgliosis ultimately alleviating neuro-inflammation. Furthermore, F-SLOH mitigates hyperphosphorylated Tau aggregates, synaptic deficits and ameliorates synaptic memory function, and cognitive impairment in AD mouse models. The mechanistic studies have shown that F-SLOH promotes the clearance of C-terminal fragment 15 (CTF15) of APP and Paired helical filaments of Tau (PHF1) in stable cell models via the activation of transcription factor EB (TFEB). Moreover, F-SLOH promotes ALP and lysosomal biogenesis for the clearance of soluble, insoluble Aβ, and phospho Tau. Our results unambiguously reveal effective etiological capabilities of theranostic F-SLOH to target and intervene multiple neuropathological changes in AD mouse models. Therefore, F-SLOH demonstrates tremendous therapeutic potential for treating AD in its early stage.

Keyword3xtg-ad 5xfad Alzheimer's Disease Aβ-aggregate Inhibition Aβ-targeting Theranostic
DOI10.1016/j.redox.2022.102280
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000791993700002
Scopus ID2-s2.0-85126116640
Fulltext Access
Citation statistics
Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorIyaswamy, Ashok; Li, Hung Wing; Wong, Man Shing; Li, Min
Affiliation1.Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, Hong Kong
2.Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, 518057, China
3.Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, Hong Kong
4.Centre for Trans-disciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
5.Division of Mycobiology and Neurodegenerative Disease Research, Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur, India
6.Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
7.State Key Lab of Quality Research in Chinese Medicine, University of Macao, Macao
8.Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
9.Department of Chemistry, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
Recommended Citation
GB/T 7714
Iyaswamy, Ashok,Wang, Xueli,Krishnamoorthi, Senthilkumar,et al. Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models[J]. Redox Biology,2022,51.
APA Iyaswamy, Ashok,Wang, Xueli,Krishnamoorthi, Senthilkumar,Kaliamoorthy, Venkatapathy,Sreenivasmurthy, Sravan G.,Kumar Durairajan, Siva Sundara,Song, Ju Xian,Tong, Benjamin Chun kit,Zhu, Zhou,Su, Cheng Fu,Liu, Jia,Cheung, King Ho,Lu, Jia Hong,Tan, Jie Qiong,Li, Hung Wing,Wong, Man Shing,&Li, Min.(2022).Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models.Redox Biology,51.
MLA Iyaswamy, Ashok,et al."Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models".Redox Biology 51(2022).
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
[Iyaswamy, Ashok]'s Articles
[Wang, Xueli]'s Articles
[Krishnamoorthi, Senthilkumar]'s Articles
Baidu academic
Similar articles in Baidu academic
[Iyaswamy, Ashok]'s Articles
[Wang, Xueli]'s Articles
[Krishnamoorthi, Senthilkumar]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Iyaswamy, Ashok]'s Articles
[Wang, Xueli]'s Articles
[Krishnamoorthi, Senthilkumar]'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.