1. bookVolume 3 (2020): Issue 2 (June 2020)
Journal Details
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First Published
30 May 2018
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English
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© 2020 Sciendo
Journal Details
License
Format
Journal
First Published
30 May 2018
Publication timeframe
1 time per year
Languages
English
Copyright
© 2020 Sciendo

Pathological aggregation and accumulation of α-synuclein in neurons play a core role in Parkinson’s disease (PD) while its overexpression is a common PD model. Autophagy-lysosomal pathways are general intraneural mechanisms of protein clearance. Earlier a suppressed autophagy in the brain of young transgenic mice overexpressing the А53Т-mutant human α-synuclein (mut(PD)) was revealed. Previous studies have recognized that Cystatin C displays protective activity against neurodegeneration. This cysteine protease inhibitor attracts particular attention as a potential target for PD treatment related to autophagy modulation. Here we evaluated the mRNA levels of Cst3 encoding Cystatin C in different brain structures of 5 m.o. mut(PD) mice at standard conditions and after the chronic treatment with a neuroprotective agent, ceftriaxone (100 mg/kg, 36 days). The inflammatory markers, namely, microglial activation by IBA1 expression and mRNA levels of two chitinases genes (Chit1, Chia1), were also assessed but no significant difference was found between control and transgenic mice. Cst3 mRNA levels were significantly reduced in the striatum and amygdala in the transgenic PD model. Furthermore, this was associated with autophagy decline and might be added to early signs of synucleinopathy development. We first demonstrated the modulation of mRNA levels of Cst3 and autophagy marker Becn1 in the brain by ceftriaxone treatment. Taken together, the results support the potential of autophagy modulation through Cystatin C at early stages of PD-like pathology.

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