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6.1 Targeting the synergy between -synuclein aggregation and ferroptosis Iron overload accelerates the formation of toxic -syn oligomers, while aberrant -syn expression disrupts iron metabolism and GSH synthesis, thereby creating a vicious cycle that enhances neuronal susceptibility to ferroptosis (Chen et al., 2025)

However, the contrasting nature of the results observed, particularly regarding the effects on cardiovascular morbidity and mortality in observational versus intervention studies, suggests that further research is warranted to support the repurposing of methotrexate for cardiovascular prevention (Table 1)

doi: 10.1016/j.freeradbiomed.2013.08.002

doi: 10.1001/jamaoncol.2021.0310 27 ChenTChenTZhangYWuKZouYBilateral effect of acupuncture on cerebrum and cerebellum in ischaemic stroke patients with hemiparesis: a randomised clinical and neuroimaging trial