Oligomeric alpha-synuclein inhibits tubulin polymerization
- PMID: 17374364
- DOI: 10.1016/j.bbrc.2007.02.163
Oligomeric alpha-synuclein inhibits tubulin polymerization
Abstract
Earlier investigations have demonstrated that tubulin co-localizes with alpha-synuclein in Lewy bodies and influences the formation of alpha-synuclein aggregation. However, it is not clear whether aggregated alpha-synuclein has any effects on the function of tubulin, i.e. tubulin polymerization, a critical mechanism by which neurons maintain their morphology and execute functions. In this study, we evaluated the effects of aggregated alpha-synuclein on tubulin polymerization in dopaminergic neurons (MES cells), along with mitochondrial function, cell morphology, and viability. The results indicate that MES cells exposed to extracellular oligomeric alpha-synuclein exhibited decreased tubulin polymerization and mitochondrial function as well as morphological alternation long before cell death. Further investigation showed that internalization of oligomeric alpha-synuclein by neurons appeared to be critical in the process, although direct interaction between tubulin and intracellular oligomeric alpha-synuclein was not necessary. Finally, we demonstrated that neurotoxicity induced by oligomeric alpha-synuclein was largely prevented by overexpressing the neuroprotective protein, DJ-1.
Similar articles
-
Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease.J Neurochem. 2008 Jun 1;105(6):2435-53. doi: 10.1111/j.1471-4159.2008.05333.x. J Neurochem. 2008. PMID: 18331584
-
Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson's disease.FASEB J. 2005 Apr;19(6):533-42. doi: 10.1096/fj.04-2751com. FASEB J. 2005. PMID: 15791003
-
The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.Hum Mol Genet. 2005 May 1;14(9):1231-41. doi: 10.1093/hmg/ddi134. Epub 2005 Mar 24. Hum Mol Genet. 2005. PMID: 15790595
-
[Parkinson's disease: what have we learned from the genes responsible for familial forms?].Med Sci (Paris). 2003 May;19(5):613-9. doi: 10.1051/medsci/2003195613. Med Sci (Paris). 2003. PMID: 12836396 Review. French.
-
[Advances in the genetic studies in Parkinson's disease].Neurol Neurochir Pol. 2004 Mar-Apr;38(2):127-36. Neurol Neurochir Pol. 2004. PMID: 15307606 Review. Polish.
Cited by
-
Reciprocal induction between α-synuclein and β-amyloid in adult rat neurons.Neurotox Res. 2013 Jan;23(1):69-78. doi: 10.1007/s12640-012-9330-y. Epub 2012 May 19. Neurotox Res. 2013. PMID: 22610785
-
Microtubule Destabilization Paves the Way to Parkinson's Disease.Mol Neurobiol. 2017 Nov;54(9):6762-6774. doi: 10.1007/s12035-016-0188-5. Epub 2016 Oct 18. Mol Neurobiol. 2017. PMID: 27757833 Review.
-
The Effect of Aggregated Alpha Synuclein on Synaptic and Axonal Proteins in Parkinson's Disease-A Systematic Review.Biomolecules. 2022 Aug 29;12(9):1199. doi: 10.3390/biom12091199. Biomolecules. 2022. PMID: 36139038 Free PMC article. Review.
-
Phosphatidylcholine and Phosphatidylserine Uniquely Modify the Secondary Structure of α-Synuclein Oligomers Formed in Their Presence at the Early Stages of Protein Aggregation.ACS Chem Neurosci. 2022 Aug 17;13(16):2380-2385. doi: 10.1021/acschemneuro.2c00355. Epub 2022 Jul 29. ACS Chem Neurosci. 2022. PMID: 35904551 Free PMC article.
-
Alpha-synuclein and intracellular trafficking: impact on the spreading of Parkinson's disease pathology.J Mol Med (Berl). 2013 Jun;91(6):693-703. doi: 10.1007/s00109-013-1038-9. Epub 2013 Apr 25. J Mol Med (Berl). 2013. PMID: 23616088 Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous
