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Prion Diseases

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Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 15))

Abstract

Prion diseases are a group of invariably fatal and transmissible neurodegenerative disorders that are associated with the misfolding of the normal cellular prion protein, with the misfolded conformers constituting an infectious unit referred to as a “prion”. Prions can spread within an affected organism by directly propagating this misfolding within and between cells and can transmit disease between animals of the same and different species. Prion diseases have a range of clinical phenotypes in humans and animals, with a principle determinant of this attributed to different conformations of the misfolded protein, referred to as prion strains. This chapter will describe the different clinical manifestations of prion diseases, the evidence that these diseases can be transmitted by an infectious protein and how the misfolding of this protein causes disease.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Aβ:

Amyloid beta

BSE:

Bovine spongiform encephalopathy

C1:

C-terminal fragment of PrP produced by α-cleavage

C2:

C-terminal fragment of PrP produced by β-cleavage

C3:

C-terminal fragment of PrP produced by γ-cleavage

Cu2+ :

Copper-II ion

CCL2:

Chemokine (Cysteine-cysteine motif) ligand 2

CCL5:

Chemokine (Cysteine-cysteine motif) ligand 5

CCR2:

Cysteine-cysteine chemokine receptor 2

CCR5:

Cysteine-cysteine chemokine receptor 5

CJD:

Creutzfeldt-Jakob disease

CNS:

Central nervous system

COCS:

Cerebellar organotypic cultured slices

CSF:

Cerebrospinal fluid

CWD:

Chronic wasting disease

D177N:

Disease-associated mutation of PrP; aspartic acid at position 177 is replaced by asparagine

EEG:

Electroencephalogram

eIF2α:

Eukaryotic translation factor-2 alpha

ER:

Endoplasmic reticulum

ERAD:

Endoplasmic-reticulum-associated protein degradation

FFI:

Fatal familial insomnia

FTIR spectroscopy:

Fourier transform infrared spectroscopy

GFAP:

Glial fibrillary acidic protein

GPI:

Glycosylphosphatidylinositol

Grp78/BiP:

78 kDa glucose-regulated protein/binding immunoglobulin protein

GSS:

Gerstmann–Sträussler–Scheinker syndrome

IL-1:

Interleukin-1

IL-10:

Interleukin-10

IL-12p40:

Interleukin-12 p40

IL-1R:

Interleukin-1 receptor

IL-1Ra:

Interleukin-1 receptor antagonist

KA:

Kainate

kDa:

Kilodalton

M:

Methionine; MM implies methionine homozygosity at position 129 of PrP

MAPK:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemoattractant protein 1

MEK:

MAPK/ERK kinase

mGluR:

Metabotropic glutamate receptors

MRI:

Magnetic resonance imaging

mRNA:

Messenger RNA

MV:

Implies methionine-valine heterozygosity at position 129 of PrP

N1:

N-terminal fragment of PrP produced by α-cleavage

N2:

N-terminal fragment of PrP produced by β-cleavage

N2a:

Murine neuroblastoma cell line

N3:

N-terminal fragment of PrP produced by γ-cleavage

NMDAR:

N-methyl-d-aspartate receptor

NMR:

Nuclear magnetic resonance spectroscopy

P101L:

Disease-associated mutation of PrP; proline at position 101 is replaced by luecine

PE:

Phosphatidylethanolamine

PERK:

Protein kinase RNA (PKR)-like ER kinase

PK:

Proteinase K

PMCA:

Protein misfolding cyclic amplification

POPG:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol

PRNP :

Gene encoding the human prion protein

Prnp−/− :

Prion protein gene knock out animals

PrP:

Prion protein

PrPC :

Normal, cellular PrP

PrPSc :

Disease-associated PrP

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

RT-QuIC:

Real time quaking induced conversion

sCJD:

Sporadic CJD

TGFβ:

Transforming growth factor beta

TNFα:

Tumour necrosis factor alpha

UK:

United Kingdom

UPR:

Unfolded protein response

USA:

United States of America

V:

Valine; VV implies valine homozygosity at position 129 of PrP

vCJD:

Variant CJD

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Authors and Affiliations

  1. Department of Pathology, The University of Melbourne, Parkville, VIC, 3010, Australia

    Benjamin C. Whitechurch B.Sc. (Hons.), Jeremy M. Welton B.Sc. (Hons.), Ph.D. & Victoria A. Lawson B.Sc. (Hons.), Ph.D.

  2. Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia

    Benjamin C. Whitechurch B.Sc. (Hons.) & Jeremy M. Welton B.Sc. (Hons.), Ph.D.

  3. Departments of Pathology and Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia

    Steven J. Collins M.B.B.S., M.D.

  4. Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia

    Steven J. Collins M.B.B.S., M.D. & Victoria A. Lawson B.Sc. (Hons.), Ph.D.

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  1. Benjamin C. Whitechurch B.Sc. (Hons.)
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  4. Victoria A. Lawson B.Sc. (Hons.), Ph.D.
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Correspondence to Victoria A. Lawson B.Sc. (Hons.), Ph.D. .

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  1. University of Melbourne Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Philip Beart

  2. Pediatrics and Pharmacology Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Michael Robinson

  3. School of Life Sciences Bradford School of Pharmacy, University of Bradford, Bradford, United Kingdom

    Marcus Rattray

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Nicholas J. Maragakis

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Whitechurch, B.C., Welton, J.M., Collins, S.J., Lawson, V.A. (2017). Prion Diseases. In: Beart, P., Robinson, M., Rattray, M., Maragakis, N. (eds) Neurodegenerative Diseases. Advances in Neurobiology, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-57193-5_13

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