A golden opportunity for the treatment of pathological muscle wasting

The title is a play on words with the abbreviated name of a protein (DOR, Diabetes and Obesity Regulated), which sounds like “d’or”, a word that in Catalan means golden. This protein, DOR, has been identified as a therapeutic target to treat muscle wasting associated to pathological conditions such as type 1 diabetes, or cachexia in patients with cancer or infectious diseases.

This is the conclusion from a study performed by scientists at the Institute for Research in Biomedicine (IRB), in Barcelona, headed by Antonio Zorzano, professor from the Department of Biochemistry and Molecular Biology at the University of Barcelona (UB), and published in the Journal of Clinical Investigation. The study indicates that DOR is a negative regulator of skeletal muscle mass that enhances basal autophagy. Autophagy is pathway that degrades long-lived proteins and organelles from the cell to maintain a correct cellular function. Thus, autophagy is like a quality control process that ensures cells stay healthy, but an excessive autophagy may cause muscle atrophy favoring muscle loss. The results of the study showed that DOR is highly repressed in muscle from type 2 diabetic patients, and the researchers propose that this repression is part of a mechanism responsible for the preservation of muscle mass in type 2 diabetes. The researchers also found that increased DOR expression in the muscle of diabetic mice leads to enhanced autophagy, which in turn favours the loss of muscle mass in these animals.

The results of the study point to DOR as a plausible target against which to develop a drug to prevent muscle deterioration in certain diseases. The advantage of developing a DOR inhibitor is that autophagy, a process necessary to keep cells healthy, would not be completely blocked in the absence of this protein. DOR is not essential for autophagy, but acts more as an accelerator. Thus, the inhibition of DOR would only partially reduce autophagy as other molecules involved would exert their activity normally, thus maintaining the levels of autophagy in a beneficial range for cells.

Marta Alegret (Universitat de Barcelona)


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