| Original language | English (US) |
|---|---|
| Pages (from-to) | 705-713 |
| Number of pages | 9 |
| Journal | Annals of neurology |
| Volume | 38 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1995 |
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
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In: Annals of neurology, Vol. 38, No. 5, 11.1995, p. 705-713.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Inclusion body myositis and myopathies
AU - Griggs, Robert C.
AU - Askanas, Valerie
AU - DiMauro, Salvatore
AU - Engel, Andrew
AU - Karpati, George
AU - Mendell, Jerry R.
AU - Rowland, Lewis P.
N1 - Funding Information: Objective: A key intracellular event in IBM pathogenic cascade is increased transcription and accumulation of amyloid-beta precursor protein, including its product A-beta. IBM vacuolated muscle fibers (VMFs) contain accumulation of free cholesterol (FC), which colocalizes with A-beta. Caveolae are plasma membrane microdomains important in maintaining FC homeostasis. Caveolin-1 (Cav-1), a major protein of caveolae, binds FC and regulates intracellular FC traffic. Expression of Cav-1 is regulated by intracellular FC level. Methods: In 10 IBM, 19 disease and 6 normal muscle biopsies, Cav-1 was studied by light-and electron-microscopic immunocytochemistry and immunoblots. Results: In IBM, 80-90% of the VMFs had plaque-like Cav-1-immunoreactive inclusions, which colocalized with accumulated FC and A-beta. By gold-immuno-EM Cav-1 was localized on amorphous, vesicular and tubular structures, and 6-10nm fibrils. None of the control muscle biopsies contained cav-1 inclusions characteristic of IBM VMFs. By immunoblots, Cav-1 migrated as a 22 kDa band and its expression was increased in IBM, as compared to controls. Conclusions: 1) Our studies provide the first demonstration of Cav-1 abnormalities in human muscle; 2) Abnormal accumulation of Cav-1, and its co-localization with FC and A-beta in IBM VMFs, suggests its novel role in IBM pathogenesis, such as possibly influencing a) abnormalities of FC trafficking, b) A-beta deposition, and c) signal transduction. Supported by: Grants from the NIH (AG16768) and the MDA, to V.Askanas
PY - 1995/11
Y1 - 1995/11
UR - http://www.scopus.com/inward/record.url?scp=0028787389&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028787389&partnerID=8YFLogxK
U2 - 10.1002/ana.410380504
DO - 10.1002/ana.410380504
M3 - Article
C2 - 7486861
AN - SCOPUS:0028787389
SN - 0364-5134
VL - 38
SP - 705
EP - 713
JO - Annals of Neurology
JF - Annals of Neurology
IS - 5
ER -