3-anhydro-6-hydroxy-ophiobolin A, a fungal sesterterpene from Bipolaris oryzae induced autophagy and promoted the degradation of α-synuclein in PC12 cells

Bioorganic & Medicinal Chemistry Letters
Danfeng XueQuan Chen

Abstract

Autophagy is defined as an evolutionarily conserved process responsible for degradation of the cytoplasmic components including protein aggregates via the lysosomal machinery. Increasing evidence has linked defective autophagic degradation of protein aggregates with the pathogenesis of neurodegenerative disorders, and it is suggested that promotion of autophagy is regarded as a potential therapeutic for these diseases including Parkinson's disease (PD). Here we identified, 3-anhydro-6-hydroxy-ophiobolin A (X15-2), an ophiobolin derivative from Bipolaris oryzae that can strongly induce autophagic degradation of α-synuclein, the major constituent of Lewy bodies. We showed that X15-2 induced autophagy is dependent on both Beclin1 and Beclin2. Knockout of ATG5 by CRISPER/Cas9 prevented X15-2 induced autophagy and degradation of α-synuclein. Mechanistically, we showed that X15-2 induces ROS and the activation of JNK signaling for the autophagic degradation of α-synuclein in PC12 cells.

References

Sep 24, 2005·Cell·Sophie PattingreBeth Levine
Sep 7, 2007·Trends in Cell Biology·Ruth Scherz-Shouval, Zvulun Elazar
Aug 18, 2010·Antioxidants & Redox Signaling·Isei Tanida
Sep 1, 2012·Nature Reviews. Drug Discovery·David C RubinszteinBeth Levine
Sep 21, 2013·Neuron·Jacob T BendorRobert H Edwards
Dec 18, 2013·Science·Ophir ShalemFeng Zhang

❮ Previous
Next ❯

Citations

Aug 18, 2016·Organic & Biomolecular Chemistry·Paolo BeuzerJames J La Clair
Sep 15, 2018·Natural Product Reports·Yuye ChenJing Xu
Jan 28, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Maria XilouriLeonidas Stefanis
Jul 19, 2017·Marine Drugs·Wei TianKui Hong
Dec 23, 2020·Natural Product Reports·Keke Li, Kirk R Gustafson
Aug 26, 2017·Chemical Reviews·David W Christianson
Aug 28, 2021·Brain Sciences·Neha MohanPeter W Baas

❮ Previous
Next ❯

Related Concepts

Related Feeds

Parkinson's Disease & Autophagy

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

© 2022 Meta ULC. All rights reserved