Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent.

Cell death & disease

PubMedID: 23303125

Jackson TC, Verrier JD, Kochanek PM. Anthraquinone-2-sulfonic acid (AQ2S) is a novel neurotherapeutic agent. Cell Death Dis. 2013;4e451.
Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid ß (Aß) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post-treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H(2)O(2)) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H(2)O(2) injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 µM) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H(2)O(2) injury at 50 and 75 µM. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor.