Mn-Induced Neurocytes Injury and Autophagy Dysfunction in Alpha-Synuclein Wild-Type and Knock-Out Mice: Highlighting the Role of Alpha-Synuclein

Neurotoxicity Research
Dong-Ying YanBin Xu

Abstract

Overexposure to manganese (Mn) is an important environmental risk factor for Parkinsonian-like symptoms referred to as manganism. Alpha-synuclein (α-Syn) oligomerization is a major cause in Mn-induced neurotoxicity. Autophagy, as an adjust response to control intracellular protein homeostasis, is involved in the degradation of α-Syn monomers or oligomers. Furthermore, autophagy dysregulation is also related to development of neurodegenerative disorders. Hence, we speculated that there was an interaction effect between α-Syn oligomerization and autophagy upon Mn exposure. In this study, we applied α-Syn gene knockout mice (α-Syn-/-) and wild-type mice (α-Syn+/+) treated with three different concentrations of MnCl2 (50, 100, and 200 μmol/kg) to elucidate the physiological role of α-Syn in Mn-induced autophagy dysregulation and neurocytes injury. We found that activation of chaperone-mediated autophagy (CMA) pathway by Mn was independent of α-Syn. Additionally, α-Syn could ameliorate excessive autophagy induced by high dose Mn (200 μmol/kg). Next, we used 5 mg/kg Rapamycin (Rap) or 3-methyladenine (3-MA) to regulate autophagy. The study revealed that autophagy is involved in Mn-induced α-Syn oligomerization and neurocytes injury. ...Continue Reading

References

Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ashish C MasseyAna Maria Cuervo
Sep 22, 2010·The Journal of Cell Biology·Ashley R WinslowDavid C Rubinsztein
May 31, 2011·Physiology & Behavior·Pascal TétreaultPhilippe Sarret
Aug 6, 2011·Journal of Applied Physiology·Kazuyuki YasuharaKatsumasa Goto
Dec 16, 2011·Autophagy·Ellen WirawanPeter Vandenabeele
Dec 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hiroshi KogaAna Maria Cuervo
Mar 28, 2013·The Journal of Biological Chemistry·Selcuk A TanikVirginia M Y Lee
Apr 23, 2013·Neurotoxicity Research·Jianbin ZhangJingyuan Chen
Jul 9, 2013·Archives of Toxicology·Saritha KrishnaNikolay M Filipov
Dec 7, 2013·Cellular Signalling·Laurence A BoothPaul Dent
Nov 25, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dilshan S HarischandraAnumantha G Kanthasamy
Mar 15, 2015·Experimental & Molecular Medicine·Aaron Ciechanover, Yong Tae Kwon
May 15, 2015·Annual Review of Nutrition·Kyle J HorningMichael Aschner
May 20, 2015·Journal of Neurochemistry·Pan ChenMichael Aschner
Aug 2, 2015·Current Environmental Health Reports·Stefanie L O'Neal, Wei Zheng
Jan 28, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Maria XilouriLeonidas Stefanis
Feb 13, 2016·Neurochemical Research·Ziyan ZhangMichael Aschner
Aug 16, 2016·Environmental Toxicology and Pharmacology·Lijuan DingJiafeng Wang
Aug 20, 2016·Frontiers in Neuroscience·Tanara Vieira PeresMichael Aschner
Oct 17, 2016·Essays in Biochemistry·Matthew P Jackson, Eric W Hewitt
Dec 13, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lu WangQi Yang
Apr 19, 2017·Current Environmental Health Reports·Anna C Pfalzer, Aaron B Bowman
Sep 4, 2017·Life Sciences·Palaniyandi RavananPriti Talwar

❮ Previous
Next ❯

Citations

Aug 18, 2020·Expert Review of Neurotherapeutics·Airton C MartinsMichael Aschner
Sep 25, 2019·International Journal of Environmental Research and Public Health·Airton Cunha MartinsMichael Aschner
Sep 5, 2019·Basic & Clinical Pharmacology & Toxicology·Kuan LiuBin Xu
Oct 13, 2020·Frontiers in Neuroscience·Dong-Ying Yan, Bin Xu
Dec 1, 2020·Biophysical Chemistry·Magdalena I IvanovaAyyalusamy Ramamoorthy
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ivan Nyarko-DanquahEunsook Lee
Feb 27, 2021·Frontiers in Aging Neuroscience·Jaione Auzmendi-Iriarte, Ander Matheu
Mar 12, 2021·Journal of Cellular Physiology·Yuping LuoMin Li
Apr 17, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Zhi-Qi LiuBin Xu
May 1, 2021·International Journal of Molecular Sciences·Alexey A TinkovMichael Aschner

❮ Previous
Next ❯

Methods Mentioned

BETA
gene knockout
PCR
co-immunoprecipitation
flow cytometry
transmission electron microscopy
electron microscopy
confocal
Co-IP
immunoprecipitation

Software Mentioned

SPSS
ImageJ
EthoVision XT

Related Concepts

Related Feeds

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

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.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

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