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Fig. 8 | Journal of Neuroinflammation

Fig. 8

From: ASC specks exacerbate α‑synuclein pathology via amplifying NLRP3 inflammasome activities

Fig. 8

ASC specks exacerbate neuronal α‑synuclein pathology via amplifying microglial NLRP3 inflammasome activities. The NLRP3 inflammasome was assembled and activated in microglia under α-synuclein PFFs stimulation. Upon the assembly of ASC with NLRP3, pro-caspase-1 was recruited, which mediated cleavage of cytokines and GSDMD, accompanied with ASC specks formation and release. ASC specks amplified NLRP3 inflammasome activation induced by α-synuclein PFFs in a vicious positive feedback manner, which significantly promoted reactive microgliosis and neuronal α-synuclein accumulation. These effects contributed to propagation of α-synuclein pathology, degeneration of dopaminergic neurons and motor deficits. Knockdown of endogenous ASC significantly suppressed microglial NLRP3 inflammasome activation and neuronal α‑synuclein aggregation under the challenge of PFFs, indicating that targeting ASC is a potentially therapeutic approach for PD

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