Fig. 8

Beclin 1 as a switch between homeostasis and apoptosis in neurodegeneration. Schematic representation of the potential roles of Beclin 1. Under homeostatic conditions (left) Beclin 1 acts as a scaffold for different protein complexes mediating various cellular processes. Long-lived proteins and organelles can be degraded in the autophagy-lysosomal degradation pathway. Beclin 1 can also regulate endocytosis and receptor recycling, crucial processes for growth factor signaling in neurons. In response to stress (right) caspases become activated and cleave Beclin 1 into N-terminal and C-terminal fragments, impairing its interactions with other proteins and homeostatic functions. Additionally, the C-terminal fragment can prime the cell for apoptotic stimuli. In the context of neurodegeneration, the C-terminal fragment can potentiate the effect of caspase activation and exacerbate apoptosis and neuronal cell death