β-Secretase 1's Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice

Frontiers in Cellular Neuroscience
Diego PiedrahitaGloria Patricia Cardona-Gómez

Abstract

β-site APP cleaving enzyme 1 (BACE1) initiates APP cleavage, which has been reported to be an inducer of tau pathology by altering proteasome functions in Alzheimer's disease (AD). However, the exact relationship between BACE1 and PHF (Paired Helical Filaments) formation is not clear. In this study, we confirm that BACE1 and Hsc70 are upregulated in the brains of AD patients, and we demonstrate that both proteins show enhanced expression in lipid rafts from AD-affected triple transgenic mouse brains. BACE1 targeting increased Hsc70 levels in the membrane and cytoplasm fractions and downregulated Hsp90 and CHIP in the nucleus in the hippocampi of 3xTg-AD mice. However, these observations occurred in a proteasome-independent manner in vitro. The BACE1miR-induced reduction of soluble hyperphosphorylated tau was associated with a decrease in MAPK activity. However, the BACE1 RNAi-mediated reduction of hyperphosphorylated tau was only blocked by 3-MA (3-methyladenine) in vitro, and it resulted in the increase of Hsc70 and LAMP2 in lipid rafts from hippocampi of 3xTg-AD mice, and upregulation of survival and homeostasis signaling. In summary, our findings suggest that BACE1 silencing neuroprotects reducing soluble hyperphosphorylated...Continue Reading

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Citations

Jul 19, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pei-Pei Guan, Pu Wang
Jul 3, 2019·Scientific Reports·Andrea CrottiRichard M Ransohoff
Nov 29, 2016·Frontiers in Cellular Neuroscience·Javier G Villamil-OrtizGloria P Cardona-Gómez
Jan 10, 2017·Frontiers in Aging Neuroscience·Gloria Patricia Cardona-Gómez, Francisco Lopera
May 25, 2021·Frontiers in Cellular Neuroscience·María Victoria Chacón-QuinteroGloria Patricia Cardona-Gómez

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Methods Mentioned

BETA
ubiquitination
transfection
PCR
transgenic
Assay
Infrared Imaging
fluorescence microscopy
immunoprecipitation
phosphotransferase
ELISA

Software Mentioned

NIH ImageJ
Pro
image Scope Pro
Cell Software
GraphPad Prism
SPSS
GraphPad
Quantity One
ImageJ
Scope

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