Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity.

Background: Aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of aliphatic aldehydes, including acetaldehyde. About 45% of Han Chinese (East Asians), accounting for 8% of humans, carry a single point mutation in ALDH2*2 (E504K) that leads to accumulation of toxic reactive aldehydes.

Methods: Sequencing of a small Mexican cohort and a search in the ExAC genomic database for additional ALDH2 variants common in various ethnic groups was set to identify missense variants.

β -adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy.

β -adrenoceptor agonists improve autophagy and re-establish proteostasis in cardiac cells; therefore, suggesting autophagy as a downstream effector of β -adrenoceptor signaling pathway. Here, we used the pharmacological and genetic tools to determine the autophagy effect of sustained β -adrenoceptor activation in rodents with neurogenic myopathy, which display impaired skeletal muscle autophagic flux. Sustained β -adrenoceptor activation using Formoterol (10 μg kg  day ), starting at the onset of neurogenic myopathy, prevents disruption of autophagic flux in skeletal muscle 14 days after sciatic nerve constriction.

Mitochondrially-targeted treatment strategies.

Disruption of mitochondrial function is a common feature of inherited mitochondrial diseases (mitochondriopathies) and many other infectious and non-infectious diseases including viral, bacterial and protozoan infections, inflammatory and chronic pain, neurodegeneration, diabetes, obesity and cardiovascular diseases. Mitochondria therefore become an attractive target for developing new therapies. In this review we describe critical mechanisms involved in the maintenance of mitochondrial functionality and discuss strategies used to identify and validate mitochondrial targets in different diseases.

Exercise prevents impaired autophagy and proteostasis in a model of neurogenic myopathy.

Increased proteolytic activity has been widely associated with skeletal muscle atrophy. However, elevated proteolysis is also critical for the maintenance of cellular homeostasis by disposing cytotoxic proteins and non-functioning organelles. We recently demonstrated that exercise activates autophagy and re-establishes proteostasis in cardiac diseases.