scholarly journals Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages

2007 ◽  
Vol 176 (7) ◽  
pp. 979-993 ◽  
Author(s):  
Sarina Meinen ◽  
Patrizia Barzaghi ◽  
Shuo Lin ◽  
Hanns Lochmüller ◽  
Markus A. Ruegg

Mutations in laminin-α2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-α2 are dystroglycan and α7β1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to α7β1 integrin, substantially ameliorates the disease (Moll, J., P. Barzaghi, S. Lin, G. Bezakova, H. Lochmuller, E. Engvall, U. Muller, and M.A. Ruegg. 2001. Nature. 413:302–307; Bentzinger, C.F., P. Barzaghi, S. Lin, and M.A. Ruegg. 2005. Matrix Biol. 24:326–332.). Now we show that late-onset expression of mini-agrin still prolongs life span and improves overall health, although not to the same extent as early expression. Furthermore, a chimeric protein containing the dystroglycan-binding domain of perlecan has the same activities as mini-agrin in ameliorating the disease. Finally, expression of full-length agrin also slows down the disease. These experiments are conceptual proof that linking the basement membrane to dystroglycan by specifically designed molecules or by endogenous ligands, could be a means to counteract MDC1A at a progressed stage of the disease, and thus opens new possibilities for the development of treatment options for this muscular dystrophy.

2017 ◽  
Vol 4 (2) ◽  
pp. 115-126 ◽  
Author(s):  
Raffaella Willmann ◽  
Heather Gordish-Dressman ◽  
Sarina Meinen ◽  
Markus A. Rüegg ◽  
Qing Yu ◽  
...  

2012 ◽  
Vol 22 (9-10) ◽  
pp. 893
Author(s):  
K.G. Meilleur ◽  
M. Jain ◽  
E. Kim ◽  
L. Hynan ◽  
C.Y. Shieh ◽  
...  

2013 ◽  
Vol 23 (9-10) ◽  
pp. 781
Author(s):  
H. Xiong ◽  
D.D. Tan ◽  
S. Wang ◽  
X.Z. Chang ◽  
Y. Yuan ◽  
...  

2005 ◽  
Vol 15 (9-10) ◽  
pp. 588-594 ◽  
Author(s):  
Mariz Vainzof ◽  
Pascale Richard ◽  
Ralf Herrmann ◽  
Cecilia Jimenez-Mallebrera ◽  
Beril Talim ◽  
...  

2000 ◽  
Vol 277 (3) ◽  
pp. 639-642 ◽  
Author(s):  
Giovanna Lattanzi ◽  
Francesco Muntoni ◽  
Patrizia Sabatelli ◽  
Stefano Squarzoni ◽  
Nadir Mario Maraldi ◽  
...  

FEBS Letters ◽  
1997 ◽  
Vol 415 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Yuko Miyagoe ◽  
Kazunori Hanaoka ◽  
Ikuya Nonaka ◽  
Michiko Hayasaka ◽  
Yoko Nabeshima ◽  
...  

2008 ◽  
Vol 65 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Mahasweta Girgenrath ◽  
Mary Lou Beermann ◽  
Vivek K. Vishnudas ◽  
Sachiko Homma ◽  
Jeffrey Boone Miller

2008 ◽  
Vol 18 (2) ◽  
pp. 137-145 ◽  
Author(s):  
Olfa Siala ◽  
Nacim Louhichi ◽  
Chahnez Triki ◽  
Madeleine Morinière ◽  
Faiza Fakhfakh ◽  
...  

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