Tau Protein as a New Regulator of Cellular Prion Protein Transcription.
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
References
Complete genomic sequence and analysis of the prion protein gene region from three mammalian species
Citations
Datasets Mentioned
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Alzheimer's Disease: Tau & TDP-43
Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.
Alzheimer's Disease: Transcription
Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.