Key result
BAG3 is a multifunctional protein whose mutations are associated with cardiomyopathy and critical limb ischemia, highlighting its potential as a therapeutic target for cardiac and skeletal muscle diseases.
Understanding the biology of the BAG3 protein highlights its potential as a therapeutic target for patients with cardiac and skeletal muscle diseases, including various cardiomyopathies.
May position BAG3 as a therapeutic target in cardiomyopathies; leaves open the need for clinical validation.
The B-cell lymphoma 2–associated anthanogene (BAG3) protein is expressed most prominently in the heart, the skeletal muscle, and in many forms of cancer. In the heart, it serves as a co-chaperone with heat shock proteins in facilitating autophagy; binds to B-cell lymphoma 2, resulting in inhibition of apoptosis; attaches actin to the Z disk, providing structural support for the sarcomere; and links the α-adrenergic receptor with the L-type Ca2+ channel. When BAG3 is overexpressed in cancer cells, it facilitates prosurvival pathways that lead to insensitivity to chemotherapy, metastasis, cell migration, and invasiveness. In contrast, in the heart, mutations in BAG3 have been associated with a variety of phenotypes, including both hypertrophic/restrictive and dilated cardiomyopathy. In murine skeletal muscle and vasculature, a mutation in BAG3 leads to critical limb ischemia after femoral artery ligation. An understanding of the biology of BAG3 is relevant because it may provide a therapeutic target in patients with both cardiac and skeletal muscle disease.
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Myers et al. (2018) conducted a review in Cardiac and skeletal muscle disease. BAG3 was evaluated. BAG3 is a multifunctional protein whose mutations are associated with cardiomyopathy and critical limb ischemia, highlighting its potential as a therapeutic target for cardiac and skeletal muscle diseases.
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