Macroautophagy as a Pathomechanism in Sporadic Inclusion Body Myositis

Jan D. Lünemann, Jens Schmidt, Marinos C. Dalakas and Christian Münz

volume 3 | issue 4

July/August 2007
Pages: 384 - 386

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:

Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

Skeletal muscle fibers show a high level of constitutive and starvation-induced macroautophagy. Sporadic Inclusion Body Myositis (sIBM) is the most common acquired skeletal muscle disease in patients above the age of 50 years and is characterized by inflammation and intracellular accumulation of aggregate-prone proteins such as amyloid precursor protein (APP)/β-amyloid, hyperphosporylated tau, and presenilin. In a recent study, we found that muscle fibers of sIBM patients show increased frequencies of Atg8/LC3⁺ autophagosomes and that intracellular APP/β-amyloid colocalized with Atg8/LC3 in degenerating fibers. Colocalization of APP/β-amyloid with LC3⁺ autophagosomes was further associated with upregulation of major histocompatibility complex (MHC) class I and class II molecules and T cell infiltration. These findings indicate that APP/β-amyloid is a substrate for autophagy in skeletal muscle fibers and suggest that degradation of aggregate-prone proteins via macroautophagy can be linked with both immune-mediated and degenerative tissue damage. A better understanding of this pathway in skeletal muscle and in the inflammatory environment of sIBM might provide a rationale for novel therapeutic strategies targeting pathogenic protein aggregation.

Addendum to:

Authors

Jan D. Lünemann

The Rockefeller University

Jens Schmidt

University of Göttingen

Marinos C. Dalakas

National Institutes of Health

Christian Münz