Extracellular vesicles derived from monomeric α-synuclein-treated microglia ameliorate neuroinflammation by delivery of miRNAs targeting PRAK

•Misfolded proteins such as α-synuclein in PD, and β-amyloid in AD usually insult microglial overactivation, comparison of the extent of microglial activation under treatments with exogenous pathological proteins may provide a better understanding of microglial inflammation in neurodegenerative diseases.•The PRAK plays an important role in microglial activation and serves as an intersection in conformationally different α-synuclein in activating microglia.•EVs from microglia treated with monomeric α-synuclein could promote anti-inflammatory microglia and most of the changed EVs-associated miRNAs targeted PRAK.•The application of PRAK inhibitor GLPG0259 in combination with EVs+ may pave the way for mitigating neuroinflammation.