Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis
Article first published online: 28 OCT 2013
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 39, Issue 7, pages 736–749, December 2013
How to Cite
Girolamo, F., Lia, A., Amati, A., Strippoli, M., Coppola, C., Virgintino, D., Roncali, L., Toscano, A., Serlenga, L. and Trojano, M. (2013), Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis. Neuropathology and Applied Neurobiology, 39: 736–749. doi: 10.1111/nan.12040
- Issue published online: 28 OCT 2013
- Article first published online: 28 OCT 2013
- Accepted manuscript online: 4 MAR 2013 06:37AM EST
- Manuscript Accepted: 22 FEB 2013
- Manuscript Received: 6 OCT 2012
- University of Bari
- Italian Ministry of the University and Scientific Research (MIUR)
- Beclin 1;
- human myopathy;
- rimmed vacuoles;
Sporadic inclusion body myositis (s-IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy–lysosome pathway contribution to rimmed vacuole accumulation.
Autophagy was studied in muscle biopsy specimens obtained from eleven s-IBM patients, one suspected hereditary IBM patient, nine patients with other inflammatory myopathies and nine non-myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy-related protein ATG5, splicing variants of microtubule-associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy–lysosome pathway.
In muscle biopsies of s-IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1+ myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI-31+ phospho-tau paired helical filaments.
The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI-31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.