Regulation of amyloid-β production by the prion protein

Griffiths, Heledd H.; Whitehouse, Isobel J.; Hooper, Nigel M.

doi:10.4161/pri.18988

Cited by 21 publications

(17 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, decreased expression of PrP C in AD cases [43] with increased levels at the start of the disease and in other neurodegenerative disorders [44,45] has been also reported. A recent study has shown regulation of A production by the prion protein [46]. Taken together, these observations suggest a protective role for PrP C in AD reinforcing the hypothesis regarding a neuroprotective function of the protein [4].…”

Section: Introductionsupporting

confidence: 72%

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

et al. 2014

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by the presence of amyloid plaques mainly consisting of hydrophobic -amyloid peptide (A) aggregates and neurofibrillary tangles (NFTs) composed principally of hyperphosphorylated tau. A oligomers have been described as the earliest effectors to negatively affect synaptic structure and plasticity in the affected brains, and cellular prion protein (PrP C ) has been proposed as receptor for these oligomers.The most widely accepted theory holds that the toxic effects of A are upstream of change in tau, a neuronal microtubule-associated protein that promotes the polymerization and stabilization of microtubules. However, tau is considered decisive for the progression of neurodegeneration, and indeed tau pathology correlates well with clinical symptoms such as dementia. Different pathways can lead to abnormal phosphorylation, and, as a consequence, tau aggregates into Paired Helical Filaments (PHF) and later on into NFTs.Reported data suggest a regulatory tendency of PrP C expression in the development of AD, and a putative relationship between PrP C and tau processing is emerging. However the role of tau/PrP C interaction in AD is poorly understood.In this study we show increased susceptibility to A derived diffusible ligands (ADDLs) in neuronal primary cultures from PrP C knock-out mice, compared to wild-type, which correlates with increased tau expression. Moreover, we found increased PrP C expression that paralleled with tau at early ages in an AD murine model, and in early Braak stages of AD in affected individuals. Taken together, these results suggest a protective role for PrP C in AD by down-regulating tau expression, and they point to this protein as being crucial in the molecular events that lead to neurodegeneration in AD.

show abstract

Section: Introductionsupporting

confidence: 72%

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Moreover, because the CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit (Chikly and Quaghebeur, 2013), our results highlight the need to define PrP C changes both directly in different regions of the brain and in the CSF in low vs. high pollution exposed children and young adults. Furthermore, since PrP C likely plays a key protective role against sporadic AD (Whitehouse et al, 2010; Griffiths et al, 2012) we will expect age-related decreases in specific regional brain areas inversely related to the development of AD hallmarks in highly exposed individuals.…”

Section: Discussionmentioning

confidence: 99%

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

Calderón‐Garcidueñas¹,

Cross²,

Franco-Lira³

et al. 2013

Front. Neurosci.

View full text Add to dashboard Cite

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrPC) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrPC and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrPC (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrPC compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.

show abstract

“…The roles of APP and PrP C in the maintenance of metal homeostasis are essential for normal brain function; therefore, a disruption of this homeostasis may trigger the degeneration of synapses and ultimately lead to the pathogenesis observed in AD or prion diseases. Recent studies demonstrate that PrP C plays critical roles in the cleavage of APP and the regulation of AβP levels [84]. PrP C reportedly attenuates the oligomerization of AβP and the neurotoxicity [85].…”

Section: Protective Substances Against Prp106-126-induced Neurotoxicitymentioning

confidence: 99%

Disruption of Metal Homeostasis and the Pathogenesis of Prion Diseases

Kawahara¹,

Tanaka²,

Mizuno³

2017

Prion - An Overview

View full text Add to dashboard Cite

Prion diseases are progressive neurodegenerative diseases that are associated with the conformational conversion of normal cellular prion protein (PrP C ) into abnormal pathogenic prion protein (PrP Sc ). PrP C is a metal-binding protein that is located in the synapse and possesses the ability to bind to various metals, including Cu, Zn, Mn and Fe. Moreover, increasing evidence suggests that PrP C plays essential roles in the maintenance of metal homeostasis in the synapse. Trace elements have a crucial influence on the conformational change of PrP C . Given that other disease-related proteins such as β-amyloid protein and its precursor protein (APP) in Alzheimer's disease also exist in the synapse and possess a metal-binding ability, an interaction between PrP and metals and between PrP and APP, may occur in the synapse; the resulting metal homeostasis may lead to the pathogenesis of prion diseases. Here, we review our studies and other new findings that inform the current understanding of the link between trace elements and physiological functions of PrP C and the neurotoxicity of PrP Sc .

show abstract

Regulation of amyloid-β production by the prion protein

Cited by 21 publications

References 74 publications

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

Disruption of Metal Homeostasis and the Pathogenesis of Prion Diseases

Contact Info

Product

Resources

About