Evidence of ER stress and UPR activation in patients with Brody disease and Brody syndrome

Brody disease (BD, OMIM #601003) is an inherited skeletal muscle disease clinically characterized by exercise-induced impairment of muscle relaxation and stiffness due to the delay in the Ca2+ re-uptake in the sarcoplasmic reticulum (SR)[1, 2]. The delayed muscle relaxation mainly affects legs, harms, hands and eyelids and usually improves after a few minutes rest [1-3]. Patients frequently report myalgia, painless or mildly painful cramps whereas recurrent rhabdomyolysis have been described in a few cases [2, 3]. A reduction in sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity characterizes the skeletal muscle of these patients [2-5]. This article is protected by copyright. All rights reserved.

[1]  Ashok Kumar,et al.  Emerging roles of ER stress and unfolded protein response pathways in skeletal muscle health and disease , 2018, Journal of cellular physiology.

[2]  M. Michalak,et al.  Ca(2+) homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling. , 2015, Biochemical and biophysical research communications.

[3]  A. Ferlini,et al.  Fourty-Four Years of Brody Disease: It is Time to Review , 2013 .

[4]  D. De Grandis,et al.  SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers. , 2013, Molecular genetics and metabolism.

[5]  B. Engelen,et al.  Brody syndrome: A clinically heterogeneous entity distinct from Brody disease A review of literature and a cross-sectional clinical study in 17 patients , 2012, Neuromuscular Disorders.

[6]  P. Walter,et al.  The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation , 2011, Science.

[7]  P. Tonin,et al.  Brody Disease: Insights Into Biochemical Features of SERCA1 and Identification of a Novel Mutation , 2010, Journal of neuropathology and experimental neurology.

[8]  M. Niwa,et al.  Intrinsic capacities of molecular sensors of the unfolded protein response to sense alternate forms of endoplasmic reticulum stress. , 2006, Molecular biology of the cell.

[9]  D. Maclennan.  Ca2+ signalling and muscle disease. , 2000, European journal of biochemistry.

[10]  P. Taschner,et al.  Mutations in the gene–encoding SERCA1, the fast–twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease , 1996, Nature Genetics.

[11]  P. Jongen,et al.  Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil. , 1994, The Journal of clinical investigation.

[12]  S. Carpenter,et al.  Myopathy caused by a deficiency of Ca2+‐adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease) , 1986, Annals of neurology.

[13]  I. Brody.  Muscle contracture induced by exercise. A syndrome attributable to decreased relaxing factor. , 1969, The New England journal of medicine.