Key result
Cardiac-specific deficiency of the co-chaperone protein BAG3 in mice leads to the development of dilated cardiomyopathy associated with the destabilization of small heat shock proteins.
This commentary highlights that BAG3 is essential for cardiac protein homeostasis, and its deficiency leads to dilated cardiomyopathy, suggesting that upregulating BAG3 could be a potential therapeutic strategy for cardiac dysfunction.
Proteinopathies are characterized by the accumulation of misfolded proteins, which ultimately interfere with normal cell function. While neurological diseases, such as Huntington disease and Alzheimer disease, are well-characterized proteinopathies, cardiac diseases have recently been associated with alterations in proteostasis. In this issue of the JCI, Fang and colleagues demonstrate that mice with cardiac-specific deficiency of the co-chaperone protein BCL2-associated athanogene 3 (BAG3) develop dilated cardiomyopathy that is associated with a destabilization of small HSPs as the result of a disrupted interaction between BAG3 and HSP70. Together, the results of this study suggest that strategies to upregulate BAG3 during cardiac dysfunction may be beneficial.
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Mizushima et al. (2017) conducted an editorial in Dilated cardiomyopathy. BAG3 deficiency or mutation vs. Wild-type BAG3 was evaluated. Cardiac-specific deficiency of the co-chaperone protein BAG3 in mice leads to the development of dilated cardiomyopathy associated with the destabilization of small heat shock proteins.
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