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Figure 2: Glucagon-like peptide-1 activity in the brain gives rise to neuroprotection, through various molecular mechanisms. The mechanisms through which GLP-1 elicits a neuroprotective effect in the brain are outlined. General mechanisms are indicated in black, with specific molecular pathways in red. GLP-1 enhances neurogenesis, neuronal cell proliferation and differentiation, as evidenced by increases in the cell proliferation markers DCX and BrdU. Stimulation of the GLP-1 receptor prevents apoptosis, with a decrease in pro-apoptotic signalling molecules caspase-3 and bax, as well as greater levels of anti-apoptotic bcl-2 observed. Favourable effects on learning and memory are also seen, as reflected by enhancements in long-term potentiation, a marker of synaptic plasticity and a major mechanism underlying the processes of memory and learning in the brain. Oxidative stress is ameliorated through a reduction in reactive oxygen species. Finally, GLP-1 lowers blood glucose levels in the brain, preventing hyperglycaemia associated inflammation and cell death during ischaemia [40]. |