Abstract

Pharmacological Modulation of Autophagy for Neuroprotection in Ischaemic Stroke

Author(s): Alex Gunn, Ayesha Singh, Aipo Diao3, Ruoli Chen

Autophagy is a highly regulated, catabolic process, through which macromolecules such as damaged organelles and proteins are degraded and recycled to maintain cellular homeostasis. Various studies have shown the role of autophagy activation in the brain cells such as astrocytes, microglia, neurons and capillary endothelial cells upon an ischaemic insult. The underlying mechanism and the role of autophagy in ischaemic stroke, however, are yet to be fully elucidated. Recent studies have suggested that insufficient or excessive autophagy results in nerve damage and cell death whereas mild/moderate autophagy has a neuroprotective effect. It has been proposed that autophagy may be a therapeutic target in stroke treatment; however, there is a lot of debate as to whether induction or diminution of autophagy plays a role in neuronal survival after cerebral ischaemia and indicate that it has a dual role depending on the time of induction of autophagy. This review has summarized the role of autophagy in ischaemic stroke and explored effects of pharmacological autophagy modulators in ischaemic stroke treatment. Further studies are needed for translating the potential therapeutic approach in stroke treatment aiming at characterizing the timing, amount and specificity of the autophagy modulation.