Apoptosis, Autophagy, Necrosis and Their Multi Galore Crosstalk in Neurodegeneration

Abstract

The progression of neurodegenerative disorders is mainly characterized by immense neuron loss and death of glial cells. The mechanisms which are active and regulate neuronal cell death are namely necrosis, necroptosis, autophagy and apoptosis. These death paradigms are governed by a set of molecular determinants that are pivotal in their performance and also exhibit remarkable overlapping functional pathways. A large number of such molecules have been demonstrated to be involved in the switching of death paradigms in various neurodegenerative diseases. In this review, we discuss various molecules and the concurrent crosstalk mediated by them. According to our present knowledge and research in neurodegeneration, molecules like Atg1, Beclin1, LC3, p53, TRB3, RIPK1 play switching roles toggling from one death mechanism to another. In addition, the review also focuses on the exorbitant number of newer molecules with the potential to cross communicate between death pathways and create a complex cell death scenario. This review highlights recent studies on the inter-dependent regulation of cell death paradigms in neurodegeneration, mediated by cross-communication between pathways. This will help in identifying potential targets for therapeutic intervention in neurodegenerative diseases.

Keywords: apoptosis; autophagy; crosstalk; necroptosis; neurodegeneration.