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TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease by Regulating the Autophagy-Lysosome Pathway.
DNA Cell Biol. 2015 Nov; 34(11):661-8.DC

Abstract

To investigate whether transcriptional factor EB (TFEB) participates in amyloid-β(1-42) (Aβ(1-42))-induced pathogenesis of Alzheimer's disease (AD) and its underlying mechanisms. Three-month-old and 8-month-old transgenic APP/PS1 AD mice and age-matched wild mice were used in this study. We found that the 8-month-old AD animals presented significantly higher deposition of Aβ(1-42) and expression of TFEB and its targeted proteins, such as LAMP-1 and cathepsin D, and autophagy-associated LC3-II and p62 in brain tissues than in others. In an in vitro study, TFEB overexpression rescued autophagic flux that blocked by Aβ(1-42) and the degradation of the absorbed Aβ(1-42), relieved Aβ(1-42)-mediated induction of overloaded autophagy. In addition, TFEB overexpression enhanced cathepsin D expression and activity, restored Aβ(1-42)-disturbed acid environment of lysosome, and promoted the fusion of autophagosomes with lysosomes. Furthermore, TFEB upregulation reduced Aβ(1-42)-induced production of malondialdehyde, oxidative carbonyl proteins, and reactive oxygen species (ROS) and cell apoptosis mainly dependent on the removal of Aβ(1-42) by the autophagy-lysosome pathway. TFEB overexpression alleviated AD progression by reducing Aβ accumulation through regulating the autophagy-lysosome pathway and reducing Aβ-induced ROS production and cell apoptosis.

Authors+Show Affiliations

Encephalopathy Therapy Area, The Affiliated Hospital of Changchun University of Chinese Medicine , Changchun Jilin, People's Republic of China .Encephalopathy Therapy Area, The Affiliated Hospital of Changchun University of Chinese Medicine , Changchun Jilin, People's Republic of China .

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26368054

Citation

Zhang, Yi-dan, and Jian-jun Zhao. "TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease By Regulating the Autophagy-Lysosome Pathway." DNA and Cell Biology, vol. 34, no. 11, 2015, pp. 661-8.
Zhang YD, Zhao JJ. TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease by Regulating the Autophagy-Lysosome Pathway. DNA Cell Biol. 2015;34(11):661-8.
Zhang, Y. D., & Zhao, J. J. (2015). TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease by Regulating the Autophagy-Lysosome Pathway. DNA and Cell Biology, 34(11), 661-8. https://doi.org/10.1089/dna.2014.2738
Zhang YD, Zhao JJ. TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease By Regulating the Autophagy-Lysosome Pathway. DNA Cell Biol. 2015;34(11):661-8. PubMed PMID: 26368054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TFEB Participates in the Aβ-Induced Pathogenesis of Alzheimer's Disease by Regulating the Autophagy-Lysosome Pathway. AU - Zhang,Yi-dan, AU - Zhao,Jian-jun, Y1 - 2015/09/14/ PY - 2015/9/15/entrez PY - 2015/9/15/pubmed PY - 2016/4/27/medline SP - 661 EP - 8 JF - DNA and cell biology JO - DNA Cell Biol VL - 34 IS - 11 N2 - To investigate whether transcriptional factor EB (TFEB) participates in amyloid-β(1-42) (Aβ(1-42))-induced pathogenesis of Alzheimer's disease (AD) and its underlying mechanisms. Three-month-old and 8-month-old transgenic APP/PS1 AD mice and age-matched wild mice were used in this study. We found that the 8-month-old AD animals presented significantly higher deposition of Aβ(1-42) and expression of TFEB and its targeted proteins, such as LAMP-1 and cathepsin D, and autophagy-associated LC3-II and p62 in brain tissues than in others. In an in vitro study, TFEB overexpression rescued autophagic flux that blocked by Aβ(1-42) and the degradation of the absorbed Aβ(1-42), relieved Aβ(1-42)-mediated induction of overloaded autophagy. In addition, TFEB overexpression enhanced cathepsin D expression and activity, restored Aβ(1-42)-disturbed acid environment of lysosome, and promoted the fusion of autophagosomes with lysosomes. Furthermore, TFEB upregulation reduced Aβ(1-42)-induced production of malondialdehyde, oxidative carbonyl proteins, and reactive oxygen species (ROS) and cell apoptosis mainly dependent on the removal of Aβ(1-42) by the autophagy-lysosome pathway. TFEB overexpression alleviated AD progression by reducing Aβ accumulation through regulating the autophagy-lysosome pathway and reducing Aβ-induced ROS production and cell apoptosis. SN - 1557-7430 UR - https://www.unboundmedicine.com/medline/citation/26368054/TFEB_Participates_in_the_Aβ_Induced_Pathogenesis_of_Alzheimer's_Disease_by_Regulating_the_Autophagy_Lysosome_Pathway_ L2 - https://www.liebertpub.com/doi/10.1089/dna.2014.2738?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -