Proteolytic processing of the prion protein in health and disease.
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Proteolytic processing of the prion protein in health and disease. / Altmeppen, Hermann C.; Puig Martorell, Berta; Dohler, Frank; Thurm, Dana Kathrin; Falker, Clemens; Krasemann, Susanne; Glatzel, Markus.
In: Am J Neurodegener Dis, Vol. 1, No. 1, 1, 2012, p. 15-31.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Proteolytic processing of the prion protein in health and disease.
AU - Altmeppen, Hermann C.
AU - Puig Martorell, Berta
AU - Dohler, Frank
AU - Thurm, Dana Kathrin
AU - Falker, Clemens
AU - Krasemann, Susanne
AU - Glatzel, Markus
PY - 2012
Y1 - 2012
N2 - A variety of physiological functions, not only restricted to the nervous system, are discussed for the cellular prion protein (PrP(C)). A prominent, non-physiological property of PrPC is the conversion into its pathogenic isoform (PrP(Sc)) during fatal, transmissible, and neurodegenerative prion diseases. The prion protein is subject to posttranslational proteolytic processing and these cleavage events have been shown i) to regulate its physiological functions, ii) to produce biologically active fragments, and iii) to potentially influence the course of prion disease. Here, we give an overview on the proteolytic processing under physiological and pathological conditions and critically review what is currently known about the three main cleavage events of the prion protein, namely ?-cleavage, ?-cleavage, and ectodomain shedding. The biological relevance of resulting fragments as well as controversies regarding candidate proteases, with special emphasis on members of the A-disintegrin-and-metalloproteinase (ADAM) family, will be discussed. In addition, we make suggestions aimed at facilitating clarity and progress in this important research field. The better understanding of this issue will not only answer basic questions in prion biology but will likely impact research on other neurodegenerative diseases as well.
AB - A variety of physiological functions, not only restricted to the nervous system, are discussed for the cellular prion protein (PrP(C)). A prominent, non-physiological property of PrPC is the conversion into its pathogenic isoform (PrP(Sc)) during fatal, transmissible, and neurodegenerative prion diseases. The prion protein is subject to posttranslational proteolytic processing and these cleavage events have been shown i) to regulate its physiological functions, ii) to produce biologically active fragments, and iii) to potentially influence the course of prion disease. Here, we give an overview on the proteolytic processing under physiological and pathological conditions and critically review what is currently known about the three main cleavage events of the prion protein, namely ?-cleavage, ?-cleavage, and ectodomain shedding. The biological relevance of resulting fragments as well as controversies regarding candidate proteases, with special emphasis on members of the A-disintegrin-and-metalloproteinase (ADAM) family, will be discussed. In addition, we make suggestions aimed at facilitating clarity and progress in this important research field. The better understanding of this issue will not only answer basic questions in prion biology but will likely impact research on other neurodegenerative diseases as well.
M3 - SCORING: Journal article
VL - 1
SP - 15
EP - 31
JO - Am J Neurodegener Dis
JF - Am J Neurodegener Dis
SN - 2165-591X
IS - 1
M1 - 1
ER -
