Shedding Light on Prion Disease

Overview

Journal Prion

Specialty Biochemistry

Date 2015 Jul 18

PMID 26186508

Citations 8

Authors

Markus Glatzel

Luise Linsenmeier

Frank Dohler

Susanne Krasemann

Berta Puig

Hermann C Altmeppen

Affiliations

Soon will be listed here.

Abstract

Proteolytic processing regulates key processes in health and disease. The cellular prion protein (PrP(C)) is subject to at least 3 cleavage events, α-cleavage, β-cleavage and shedding. In contrast to α- and β-cleavage where there is an ongoing controversy on the identity of relevant proteases, the metalloprotease ADAM10 represents the only relevant PrP sheddase. Here we focus on the roles that ADAM10-mediated shedding of PrP(C) and its pathogenic isoform (PrP(Sc)) might play in regulating their physiological and pathogenic functions, respectively. As revealed by our recent study using conditional ADAM10 knockout mice (Altmeppen et al., 2015), shedding of PrP seems to be involved in key processes of prion diseases. These aspects and several open questions arising from them are discussed. Increased knowledge on this topic can shed new light on prion diseases and other neurodegenerative conditions as well.

Citing Articles

Human prion diseases and the prion protein - what is the current state of knowledge?.

Nafe R, Arendt C, Hattingen E Transl Neurosci. 2023; 14(1):20220315.

PMID: 37854584 PMC: 10579786. DOI: 10.1515/tnsci-2022-0315.

Prion Protein: The Molecule of Many Forms and Faces.

Kovac V, Serbec V Int J Mol Sci. 2022; 23(3).

PMID: 35163156 PMC: 8835406. DOI: 10.3390/ijms23031232.

Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review.

Dexter E, Kong Q Expert Rev Neurother. 2021; 21(9):969-982.

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GPI-anchor signal sequence influences PrPC sorting, shedding and signalling, and impacts on different pathomechanistic aspects of prion disease in mice.

Puig B, Altmeppen H, Linsenmeier L, Chakroun K, Wegwitz F, Piontek U PLoS Pathog. 2019; 15(1):e1007520.

PMID: 30608982 PMC: 6334958. DOI: 10.1371/journal.ppat.1007520.

Alterations in the brain interactome of the intrinsically disordered N-terminal domain of the cellular prion protein (PrPC) in Alzheimer's disease.

Ulbrich S, Janning P, Seidel R, Matschke J, Gonsberg A, Jung S PLoS One. 2018; 13(5):e0197659.

PMID: 29791485 PMC: 5965872. DOI: 10.1371/journal.pone.0197659.

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