Potential approaches for heterologous prion protein treatment of prion diseases

Davis M. Seelig, Patricia A. Goodman, Pamela J. Skinner

Research output: Contribution to journalComment/debate

5 Citations (Scopus)

Abstract

Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system.

Original languageEnglish (US)
Pages (from-to)18-24
Number of pages7
JournalPrion
Volume10
Issue number1
DOIs
StatePublished - Jan 2 2016

Fingerprint

Prion Diseases
Prions
PrPC Proteins
Peptide Hydrolases
Neurodegenerative diseases
Scrapie
Pathology
Cricetinae
Neurodegenerative Diseases
Action Potentials
Rabbits
Peptides
Prion Proteins

Keywords

  • PrP
  • PrP
  • heterologous prion proteins
  • prion
  • treatment

Cite this

Potential approaches for heterologous prion protein treatment of prion diseases. / Seelig, Davis M.; Goodman, Patricia A.; Skinner, Pamela J.

In: Prion, Vol. 10, No. 1, 02.01.2016, p. 18-24.

Research output: Contribution to journalComment/debate

@article{c3a7934418fa4d75b2cb90b3733914a4,
title = "Potential approaches for heterologous prion protein treatment of prion diseases",
abstract = "Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system.",
keywords = "PrP, PrP, heterologous prion proteins, prion, treatment",
author = "Seelig, {Davis M.} and Goodman, {Patricia A.} and Skinner, {Pamela J.}",
year = "2016",
month = "1",
day = "2",
doi = "10.1080/19336896.2015.1123372",
language = "English (US)",
volume = "10",
pages = "18--24",
journal = "Prion",
issn = "1933-6896",
publisher = "Landes Bioscience",
number = "1",

}

TY - JOUR

T1 - Potential approaches for heterologous prion protein treatment of prion diseases

AU - Seelig, Davis M.

AU - Goodman, Patricia A.

AU - Skinner, Pamela J.

PY - 2016/1/2

Y1 - 2016/1/2

N2 - Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system.

AB - Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrPC) into a protease resistant infectious form (PrPres). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrPC and PrPres. In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system.

KW - PrP

KW - PrP

KW - heterologous prion proteins

KW - prion

KW - treatment

UR - http://www.scopus.com/inward/record.url?scp=84962338694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962338694&partnerID=8YFLogxK

U2 - 10.1080/19336896.2015.1123372

DO - 10.1080/19336896.2015.1123372

M3 - Comment/debate

C2 - 26636482

AN - SCOPUS:84962338694

VL - 10

SP - 18

EP - 24

JO - Prion

JF - Prion

SN - 1933-6896

IS - 1

ER -