Myositis facilitates preclinical accumulation of pathological prion protein in muscle
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Myositis facilitates preclinical accumulation of pathological prion protein in muscle. / Neumann, Melanie; Krasemann, Susanne; Schröck, Katharina; Steinbach, Karin; Glatzel, Markus.
In: ACTA NEUROPATHOL COM, Vol. 1, No. 1, 01.01.2013, p. 78.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Myositis facilitates preclinical accumulation of pathological prion protein in muscle
AU - Neumann, Melanie
AU - Krasemann, Susanne
AU - Schröck, Katharina
AU - Steinbach, Karin
AU - Glatzel, Markus
PY - 2013/1/1
Y1 - 2013/1/1
N2 - BACKGROUND: In human and animal prion diseases, pathological prion protein, PrPSc, as well as prion infectivity is mainly found in the central nervous system, but also in lymphoid organs and muscle. Pathophysiology of prion colonization of lymphoid organs has been studied intensively, yet how myositis influences prion accumulation in muscle is unknown.RESULT: We have investigated the influence of myositis on PrPSc accumulation and prion infectivity in two distinct mouse models of experimental autoimmune myositis. Furthermore, we have addressed the relevance of PrPC expression in the lymphoreticular system in myositis by generating bone marrow chimeras.Here we show that myositis positively influences muscular PrPSc accumulation at preclinical time points and that PrPC-expression in the lymphoid system is critical for this. In muscle, PrPSc and prion infectivity are uncoupled with detectable PrPSc but no prion infectivity at preclinical time points. Muscle has an intrinsically high ability to clear PrPSc once myositis has ceased, possibly involving autophagy.CONCLUSION: Our findings provide new insights into the pathophysiology of prion colonization in muscle pointing out that myositis leads to enhanced prion colonization of muscle in subclinical prion disease.
AB - BACKGROUND: In human and animal prion diseases, pathological prion protein, PrPSc, as well as prion infectivity is mainly found in the central nervous system, but also in lymphoid organs and muscle. Pathophysiology of prion colonization of lymphoid organs has been studied intensively, yet how myositis influences prion accumulation in muscle is unknown.RESULT: We have investigated the influence of myositis on PrPSc accumulation and prion infectivity in two distinct mouse models of experimental autoimmune myositis. Furthermore, we have addressed the relevance of PrPC expression in the lymphoreticular system in myositis by generating bone marrow chimeras.Here we show that myositis positively influences muscular PrPSc accumulation at preclinical time points and that PrPC-expression in the lymphoid system is critical for this. In muscle, PrPSc and prion infectivity are uncoupled with detectable PrPSc but no prion infectivity at preclinical time points. Muscle has an intrinsically high ability to clear PrPSc once myositis has ceased, possibly involving autophagy.CONCLUSION: Our findings provide new insights into the pathophysiology of prion colonization in muscle pointing out that myositis leads to enhanced prion colonization of muscle in subclinical prion disease.
U2 - 10.1186/2051-5960-1-78
DO - 10.1186/2051-5960-1-78
M3 - SCORING: Journal article
C2 - 24299111
VL - 1
SP - 78
JO - ACTA NEUROPATHOL COM
JF - ACTA NEUROPATHOL COM
SN - 2051-5960
IS - 1
ER -