Pathologist Keqiang Ye and colleagues recently published a paper in PNAS that may have implications for Parkinson’s disease pathology and treatment strategies.
The protein alpha-synuclein is a bad actor in PD (nice explainer from Michael J. Fox Foundation); it’s a major constituent of Lewy bodies, the protein clumps that appear in PD patients’ brains, and there is a genetic link too. Alpha-synuclein seems to bring other proteins into the clumps, which may disrupt neuron function.
In particular, it sequesters PIKE-L, an inhibitor of AMP kinase, leading to AMP kinase hyperactivation and cell death. AMP kinase is a metabolic regulator activated by metformin, a common treatment for diabetes. So activating AMP kinase in some situations can be good for your body; however for the neurons affected by alpha-synuclein, activating it too much is bad.