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Evolutionarily, the origin of RCD, in particular, apoptosis has been postulated to be associated with endosymbiosis, i.e., domestication of mitochondria [137,138,139]

At excitatory and inhibitory synapses this mediates short-term synaptic plasticity and long term depression (Gerdeman et al., 2002

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Taken together, GLP-1based and dual GLP-1/GIP agonists represent a biologically plausible and clinically feasible strategy for repurposing as adjunctive neuroprotective therapies in PD, although further preclinical and clinical studies are needed to define their optimal dosing, treatment duration, and combinational approaches to ensure sustained neuroprotection (Figure 2)

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