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Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
11:29

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain

Published on: October 3, 2012

Insoluble cellular prion protein and its association with prion and Alzheimer diseases

Wen-Quan Zou1, Xiaochen Zhou, Jue Yuan

  • 1Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA. wenquan.zou@case.edu

Prion
|August 18, 2011
PubMed

Insights

Cellular prion protein (PrP(C)) has dual roles in cognition. Its conformation dictates whether PrP(C) is beneficial or detrimental, with insoluble PrP(C) linked to prion and Alzheimer diseases.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Prion Biology

Background:

  • Soluble cellular prion protein (PrP(C)) is known for its role in prion disease (PrD) via conversion to insoluble PrP(Sc).
  • PrP(C) also exhibits deleterious effects independent of PrP(Sc) in PrD and Alzheimer disease (AD), both impacting cognition.
  • PrP(C) has physiological functions, including involvement in cognitive processes.

Purpose of the Study:

  • To highlight evidence of PrP involvement in beneficial and deleterious pathways affecting cognition.
  • To hypothesize that PrP(C)'s conformation determines its beneficial or detrimental effects.
  • To propose that insoluble PrP(C) (iPrP(C)) is associated with PrD and AD.

Main Methods:

  • Identification of an insoluble PrP(C) conformer (iPrP(C)) in uninfected brains.
  • Comparison of iPrP(C) immunoreactivity and fragmentation with PrP(Sc) species in variably protease-sensitive prionopathy.
  • Observation of iPrP(C) interaction with amyloid-beta (Aβ) in AD.

Main Results:

  • An insoluble PrP(C) conformer (iPrP(C)) was identified in uninfected human and animal brains.
  • iPrP(C) shares characteristics with PrP(Sc) in variably protease-sensitive prionopathy.
  • iPrP(C) is the primary PrP species interacting with Aβ in AD.

Conclusions:

  • PrP(C)'s beneficial and deleterious effects in cognition are linked to its conformational flexibility.
  • The insoluble PrP(C) (iPrP(C)) conformer is associated with prion disease and Alzheimer disease.
  • Understanding PrP(C) conformation is crucial for deciphering its role in neurological disorders.

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