Tissue plasminogen activator mediates deleterious complement cascade activation in stroke.

The use of intravenous tissue plasminogen activator (tPA) in the treatment of ischemic stroke is limited by its propensity to exacerbate brain edema and hemorrhage. The mechanisms underlying these deleterious effects of tPA remain incompletely understood. The purpose of this study was to delineate a pathway of tPA-mediated complement cascade activation in stroke and to determine whether complement inhibition ameliorates the adverse effects of post-ischemic tPA administration.

The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models.

Inhibition of sirtuin 2 (SIRT2) deacetylase mediates protective effects in cell and invertebrate models of Parkinson's disease and Huntington's disease (HD). Here we report the in vivo efficacy of a brain-permeable SIRT2 inhibitor in two genetic mouse models of HD. Compound treatment resulted in improved motor function, extended survival, and reduced brain atrophy and is associated with marked reduction of aggregated mutant huntingtin, a hallmark of HD pathology.