Investigating the mechanism of (-)Schisandrin B on the treatment of Parkinson's disease via regulating ATG16L1/NLRP3 signalling pathway

Project: Research project

Project Details


1: To evaluate the neuroprotective effects of (-)Sch B via ATG16L1-mediated autophagy in lipopolysaccharide (LPS)/ α-syn induced model of NLRP3 inflammasome in microglia cultures.
2: To determine the molecular mechanisms by which (-)Sch B upregulates ATG16L1 expression.
3: To evaluate the protective effects of (-)Sch B in the PD model induced by stereotaxic injection of α-synuclein pre-formed fibril (PFF) in vivo.
Hypothesis to be tested: (-)Sch B improves PD by enhancing ATG16L1-mediated autophagy, inhibiting α-syn-induced autophagy deficiency and NLRP3 inflammasome activation
Design and subjects: We will determine the effects of (-)Sch B on inhibiting NLRP3 inflammasome activation and neurotoxicity induced by aggregated α-syn, and examine the molecular mechanisms by which (-)Sch B upregulates ATG16L1 expression. In addition, we will employ the PFF-α-synuclein model to evaluate the effects of (-)Sch B on autophagy, α-synuclein degradation, and neuroinflammation.
Instruments: Cell and molecular biology experiments, and animal motor behaviour tests will be employed
Interventions: PD model was induced by stereotaxic injection of α-synuclein in male C57BL/6 mice and adeno-associated virus (AAV)-shAtg16l1 will be injected into unilateral substantia nigra. (-)Sch B will be orally administered for 10 weeks.
Main outcome measures: Investigation of novel pharmacological effects of (-)Sch B and evaluate its pre-clinical efficacy in PD.
Expected results: (-)Sch B may promote the degradation of α-synuclein aggregates and inhibit the α-synuclein-induced NLRP3 inflammasome activation by enhancing ATG16L1-mediated autophagy in vitro and in vivo.

StatusNot started
Effective start/end date9/10/248/10/27


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