Role of Academia: Drug Repurposing to Induce Autophagy for Treatment of Neurodegenerative Diseases

Abstract

The prevalence of neurodegenerative diseases is increasing as the global population ages, and currently none of these late-onset conditions are curable. Therefore, there is an urgent need to understand the mechanisms of disease progression and to find new therapies. Most late-onset neurodegenerative disorders manifest with toxic, aggregate-prone proteins in neurons. Many of these harmful proteins have been shown to be autophagic substrates, and the induction of autophagy reduces their levels and attenuates disease phenotypes in neurodegenerative disease animal models. We and others have examined if existing drugs can be repurposed as new therapeutic agents that induce autophagy to reduce the levels of such toxic proteins. We highlight that a key component of a repurposing project is to test if the drug exposures at conventional doses in humans enable induction of the novel potentially therapeutic repurposing pathway.