Journal
AUTOPHAGY
Volume 18, Issue 3, Pages 559-575Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1937897
Keywords
Alpha-synuclein; autophagy flux; Parkinson disease; piperine; tandem mass tag proteomics
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Funding
- National Natural Science Foundation of China [81870994]
- National Key Plan for Scientific Research and Development of China [2016YFC1306000]
- Beijing Municipal Commission of Health and Family Planning
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This study demonstrates that piperine exerts neuroprotective effects in Parkinson's disease models by promoting autophagy flux and degradation of pathological SNCA, suggesting it may be an effective agent for PD treatment.
Olfactory dysfunction, one of the earliest non-motor symptoms of Parkinson disease (PD), is accompanied by abnormal deposition of SNCA/alpha-synuclein in the olfactory bulb (OB). The macroautophagy/autophagy-lysosome pathway (ALP) plays an important role in degrading pathological SNCA and modulating this pathway may be a promising treatment strategy. P2RX4 (purinergic receptor P2X, ligand-gated ion channel 4), a member of the purinergic receptor X family, is a key molecule regulating ALP. Piperine (PIP) is a Chinese medicine with anti-inflammatory and anti-oxidant effects. The present study investigated the neuroprotective effects of PIP on SNCA overexpression-induced PD cell and mouse models. We found that PIP oral administration (25, 50 and 100 mg/kg) for 6 weeks attenuated olfactory deficits and delayed motor deficits in Thy 1-SNCA transgenic mice overexpressing human SNCA. This was accompanied by a degradation of pathological SNCA in OB. In addition, PIP improved cell viability and promoted degradation of human SNCA in SK-N-SH cells. These protective effects were exerted via autophagy flux promotion by enhancing autophagosome-lysosome membrane fusion. Furthermore, tandem mass tag proteomics analyses showed that P2RX4 plays an important role in PIP treatment-induced activation of autophagy flux. These findings demonstrate that PIP exerts neuroprotective effects in PD models via promotion of autophagy flux and may be an effective agent for PD treatment.
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