Details

Autor(en) / Beteiligte

• Lidón, Laia
• Vergara, Cristina
• Ferrer, Isidro
• Hernández, Félix
• Ávila, Jesús
• del Rio, Jose A.
• Gavín, Rosalina

Titel

Tau Protein as a New Regulator of Cellular Prion Protein Transcription

Ist Teil von

• Molecular neurobiology, 2020-10, Vol.57 (10), p.4170-4186

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2020

Quelle

SpringerLink

Beschreibungen/Notizen

• Cellular prion protein (PrP C ) is largely responsible for transmissible spongiform encephalopathies (TSEs) when it becomes the abnormally processed and protease resistant form PrP SC . Physiological functions of PrP C include protective roles against oxidative stress and excitotoxicity. Relevantly, PrP C 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 PrP C . However, the factors responsible for the upregulation of PrP C are unknown. Thus, the aim of this study was to uncover the different molecular actors promoting PrP C 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 revealed that tau is a new modulator of PrP C expression independently of ADDL treatment and ROS levels. Lastly, we discovered that the JNK/c-jun-AP-1 pathway is involved in increased PRNP transcription activity by tau but not in the promoter response to ROS.