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Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K.
Neurotoxicology. 2011 Dec; 32(6):857-63.N

Abstract

α-Synuclein (α-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). α-Syn has been extensively studied in many neuronal cell-based PD models but has yielded mixed results. The objective of this study was to re-evaluate the dual cytotoxic/protective roles of α-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial α-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type α-Syn attenuated rotenone and maneb-induced cell death along with an attenuation of toxin-induced mitochondrial membrane potential changes and Reactive Oxygen Species level, whereas the mutant α-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type α-Syn but not the mutant variants was found to rescue cells from subsequent acute hydrogen peroxide insult. These results suggest that the fundamental property of wild type α-Syn may be protective, and such property may be lost by its familial PD mutations.

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Authors+Show Affiliations

Choong CJ
Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Perak Campus, 31900 Kampar, Perak, Malaysia.
Say YH
No affiliation info available

MeSH

Cell DeathCell Line, TumorCytoprotectionDopamineDose-Response Relationship, DrugHumansHydrogen PeroxideManebMembrane Potential, MitochondrialMutagenesis, Site-DirectedMutationNeuronsOxidative StressParkinson DiseaseReactive Oxygen SpeciesRotenoneTransfectionalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21658409

Citation

Choong, Chi-Jing, and Yee-How Say. "Neuroprotection of Α-synuclein Under Acute and Chronic Rotenone and Maneb Treatment Is Abolished By Its Familial Parkinson's Disease Mutations A30P, A53T and E46K." Neurotoxicology, vol. 32, no. 6, 2011, pp. 857-63.
Choong CJ, Say YH. Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K. Neurotoxicology. 2011;32(6):857-63.
Choong, C. J., & Say, Y. H. (2011). Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K. Neurotoxicology, 32(6), 857-63. https://doi.org/10.1016/j.neuro.2011.05.012
Choong CJ, Say YH. Neuroprotection of Α-synuclein Under Acute and Chronic Rotenone and Maneb Treatment Is Abolished By Its Familial Parkinson's Disease Mutations A30P, A53T and E46K. Neurotoxicology. 2011;32(6):857-63. PubMed PMID: 21658409.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotection of α-synuclein under acute and chronic rotenone and maneb treatment is abolished by its familial Parkinson's disease mutations A30P, A53T and E46K. AU - Choong,Chi-Jing, AU - Say,Yee-How, Y1 - 2011/05/30/ PY - 2011/02/16/received PY - 2011/03/31/revised PY - 2011/05/23/accepted PY - 2011/6/11/entrez PY - 2011/6/11/pubmed PY - 2012/5/4/medline SP - 857 EP - 63 JF - Neurotoxicology JO - Neurotoxicology VL - 32 IS - 6 N2 - α-Synuclein (α-Syn) plays a crucial role in the pathophysiology of Parkinson's disease (PD). α-Syn has been extensively studied in many neuronal cell-based PD models but has yielded mixed results. The objective of this study was to re-evaluate the dual cytotoxic/protective roles of α-Syn in dopaminergic SH-SY5Y cells. Stable SH-SY5Y cells overexpressing wild type or familial α-Syn mutants (A30P, E46K and A53T) were subjected to acute and chronic rotenone and maneb treatment. Compared with untransfected SH-SY5Y cells, wild type α-Syn attenuated rotenone and maneb-induced cell death along with an attenuation of toxin-induced mitochondrial membrane potential changes and Reactive Oxygen Species level, whereas the mutant α-Syn constructs exacerbated environmental toxins-induced cytotoxicity. After chronic treatment, wild type α-Syn but not the mutant variants was found to rescue cells from subsequent acute hydrogen peroxide insult. These results suggest that the fundamental property of wild type α-Syn may be protective, and such property may be lost by its familial PD mutations. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/21658409/Neuroprotection_of_α_synuclein_under_acute_and_chronic_rotenone_and_maneb_treatment_is_abolished_by_its_familial_Parkinson's_disease_mutations_A30P_A53T_and_E46K_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(11)00101-X DB - PRIME DP - Unbound Medicine ER -