Alda-1 is a potent ALDH2 Agonist
Posted On 2021-12-30
Aldehyde dehydrogenase 2 (ALDH2) is ubiquitously found in various tissues, including the heart, brain, and skeletal muscle, and highly expressed in the mitochondria. Many cellular functions show relations with ALDH2. They include detoxification of aldehydes, cell survival, cell proliferation, and apoptosis. The deficiency of ALDH2 causes the accumulation of cytotoxic aldehydes. It also causes oxidative stress and ER stress. However, it does not know about ALDH2 activation-induced protective effect in tendinopathy. Tendinopathy is a common musculoskeletal disease in the elderly population and athletes. It causes pain and results in the dysfunction of tendons and disability. The prevalence of tendinopathy is accounted for approximately 30% of clinical musculoskeletal consultations. Achilles tendons are the strongest and largest in all of the tendons. Achilles tendinopathy is the most common tendinopathy of the lower extremity. Thus, the prevention and treatment of tendinopathy are important issues. Alda-1 ameliorates Achilles tendinopathy in cellular and mouse models.
Alda-1 is a selective and potent agonist of ALDH2. It specifically binds to ALDH2 and activates the enzyme activity of ALDH2. Moreover, Alda-1 attenuates H2O2-induced cell death of cultured Achilles tenocytes. It also prevents H2O2-induced oxidative stress and depolarization of mitochondrial membrane potential in tenocytes. Application of Alda-1 attenuated H2O2-triggered mitochondria- and ER stress-mediated apoptotic cascades in cultured tenocytes. In addition, Alda-1 prevents H2O2-induced pathological histological features of Achilles tendons, apoptotic death of Achilles tenocytes. It also upregulates expression of inflammatory cytokines IL-1β and TNF-α.
In summary, Alda-1 is a potent agonist of ALDH2. It ameliorates H2O2-induced Achilles tendinopathy. Alda-1 can prevent and treat Achilles tendinopathy.
Liu YC, et al. Biochem Pharmacol. 2020;175:113919.