Related Experiment Videos
Prion protein is abnormally accumulated in inclusion-body myositis
V Askanas1, M Bilak, W K Engel
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90017.
Abstract:
In muscle biopsies of 8 sporadic inclusion-body myositis (S-IBM) and 4 hereditary inclusion-body myopathy (H-IBM) patients, vacuolated muscle fibers contained within their vacuoles strongly immunoreactive inclusions with 2 polyclonal and 1 monoclonal antibodies against prion protein (PrP). By light-microscopy, PrP deposits co-localized with beta-amyloid protein (A beta) and ubiquitin (Ub). By immuno-electronmicroscopy, both PrP and A beta were present on amorphous material and on 6-10 nm amyloid-like fibrils; and PrP and Ub co-localized on cytoplasmic twisted tubulofilaments (TTFs) and on amorphous material. Our study provides the first demonstration of abnormally accumulated PrP in pathological tissue other than brain, and it suggests that PrP may play a role in the pathogenesis of IBM.
Insights
Prion protein (PrP) was found in muscle fibers of inclusion-body myositis patients, co-localizing with beta-amyloid and ubiquitin. This suggests a potential role for PrP in the disease
Area of Science:
- Neurology
- Protein biochemistry
- Muscle pathology
Background:
- Inclusion-body myositis (IBM) is a progressive muscle-wasting disease.
- The exact molecular mechanisms underlying IBM pathogenesis remain unclear.
- Abnormal protein aggregation is a hallmark of many neurodegenerative diseases.
Purpose of the Study:
- To investigate the presence and localization of prion protein (PrP) in muscle biopsies from patients with sporadic IBM (S-IBM) and hereditary IBM (H-IBM).
- To determine the co-localization of PrP with other pathological markers like beta-amyloid (A beta) and ubiquitin (Ub) in IBM muscle fibers.
- To explore the potential role of PrP in the pathogenesis of IBM.
Main Methods:
- Analysis of muscle biopsies from 8 S-IBM and 4 H-IBM patients.
- Immunohistochemistry using antibodies against PrP, A beta, and Ub.
- Light and immuno-electron microscopy to visualize protein deposits and fibrils.
Main Results:
- Vacuolated muscle fibers in IBM patients showed strong immunoreactivity for PrP.
- PrP deposits co-localized with A beta and Ub in muscle fibers.
- PrP and A beta were found on amorphous material and amyloid-like fibrils.
- PrP and Ub were observed on cytoplasmic twisted tubulofilaments (TTFs).
Conclusions:
- This study demonstrates abnormal accumulation of PrP in pathological tissue outside the brain for the first time.
- The findings suggest that PrP may be involved in the pathogenesis of inclusion-body myositis.
- PrP aggregation alongside A beta and Ub in muscle fibers highlights potential shared pathways in proteinopathies.