Myositis facilitates preclinical accumulation of pathological prion protein in muscle

Abstract

BackgroundIn 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.ResultWe 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-5960-1-78) contains supplementary material, which is available to authorized users.

Enfermedades priónicas y enfermedades similares a priones

“…56 Así bien, Neumann y colegas mencionan que la PrPsc puede empezar a acumularse desde la etapa preclínica en músculos, y que en modelos de animales puede ser facilitada por una miositis que se relaciona a la llegada de PrPc a través de células del sistema linforreticular. 57 Esto se suma a los reportes de depósitos de PrPSc en músculos de pacientes humanos con CJD variante, iatrogénica y esporádica, así como en la enfermedad crónica degenerativa en cérvidos. 58 En conjunto estos datos pueden indicar la acumulación de PrPSc en los músculos de animales y humanos que padecen enfermedades priónicas, pero es necesario hacer investigaciones sobre el tema.…”