Endoplasmic reticulum-stress and unfolded protein response-activation in immune-mediated necrotizing myopathy.

Patients suffering from immune-mediated necrotizing myopathies (IMNM) harbor, the pathognomonic myositis-specific auto-antibodies anti-SRP54 or -HMGCR, while about one third of them do not. Activation of chaperone-assisted autophagy was described as being part of the molecular etiology of IMNM. Endoplasmic reticulum (ER)/sarcoplasmic reticulum (SR)-stress accompanied by activation of the unfolded protein response (UPR) often precedes activation of the protein clearance machinery and represents a cellular defense mechanism toward restoration of proteostasis.

Sequestosome-1 (p62) expression reveals chaperone-assisted selective autophagy in immune-mediated necrotizing myopathies.

Diffuse myofiber necrosis in the context of inflammatory myopathy is the hallmark of immune-mediated necrotizing myopathy (IMNM). We have previously shown that skeletal muscle fibers of IMNM patients may display nonrimmed vacuoles and sarcoplasmic irregularities. The dysfunctional chaperone activity has been linked to the defective assembly of skeletal muscle proteins and their degradation via lysosomes, autophagy and the proteasomal machinery.

PD1 pathway in immune-mediated myopathies: Pathogenesis of dysfunctional T cells revisited.

Objective: To investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and myositis induced by immune checkpoint inhibitors (irMyositis).

Methods: Skeletal muscle biopsies from 12 patients with IMNM, 7 patients with sIBM, and 8 patients with irMyositis were analyzed by immunostaining and immunofluorescence as well as by quantitative PCR.

Do tetracyclines and erythromycin exert anti-acne effects by inhibition of P450-mediated degradation of retinoic acid?

For decades, retinoic acid (RA) is known as the most potent therapeutic option in the therapy of acne and altered homeostasis of endogenous retinoids has been discussed in the context of acne pathogenesis. Besides retinoids, antibiotics such as tetracyclines or erythromycin are well established in acne pharmacotherapy. Accumulating evidence points towards common molecular pathways being targeted by both RA and anti-acne antibiotics; however, a precise 'common denominator' connecting these chemically diverse anti-acne agents has not yet been identified.