Tau Protein as a New Regulator of Cellular Prion Protein Transcription.

Molecular Neurobiology
Laia LidónRosalina Gavín

Abstract

Cellular prion protein (PrPC) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrPSC. Physiological functions of PrPC include protective roles against oxidative stress and excitotoxicity. Relevantly, PrPC downregulates tau levels, whose accumulation and modification are a hallmark in the advance of Alzheimer's disease (AD). In addition to the accumulation of misfolded proteins, in the initial stages of AD-affected brains display both increased reactive oxygen species (ROS) markers and levels of PrPC. However, the factors responsible for the upregulation of PrPC are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrPC overexpression. In order to mimic early stages of AD, we used β-amyloid-derived diffusible ligands (ADDLs) and tau cellular treatments, as well as ROS generation, to elucidate their particular roles in human PRNP promoter activity. In addition, we used specific chemical inhibitors and site-specific mutations of the PRNP promoter sequence to analyze the contribution of the main transcription factors involved in PRNP transcription under the analyzed conditions. Our results revea...Continue Reading

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Citations

Jun 3, 2021·International Journal of Molecular Sciences·Laia LidónRosalina Gavín
Jul 12, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Hanna NieznanskaKrzysztof Nieznanski

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Datasets Mentioned

BETA
Ac

Methods Mentioned

BETA
transgenic
fluorescence microscopy
transfection
transmission electron microscopy
confocal microscopy

Software Mentioned

Prism
Fiji
[UNK]
GraphPad
ZEN Blue Edition

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