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Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP.
J Neurobiol. 2002 Oct; 53(1):1-10.JN

Abstract

Mutations in the alpha-synuclein gene are linked to a rare dominant form of familial Parkinson's disease, and alpha-synuclein is aggregated in Lewy bodies of both sporadic and dominant Parkinson's disease. It has been proposed that mutated alpha-synuclein causes dopaminergic neuron loss by enhancing the vulnerability of these neurons to a variety of insults, including oxidative stress, apoptotic stimuli, and selective dopaminergic neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test this hypothesis in vivo, we overexpressed human alpha-synuclein(A53T) in the substantia nigra of normal and MPTP-treated mice by rAAV-mediated gene transfer. Determination of dopaminergic neuron survival, striatal tyrosine hydroxylase fiber density, and striatal content of dopamine and its metabolites in rAAV-injected and uninjected hemispheres demonstrated that alpha-synuclein(A53T) does not increase the susceptibility of dopaminergic neurons to MPTP. Our findings argue against a direct detrimental role for (mutant) alpha-synuclein in oxidative stress and/or apoptotic pathways triggered by MPTP, but do not rule out the possibility that alpha-synuclein aggregation in neurons exposed to oxidative stress for long periods of time may be neurotoxic.

Authors+Show Affiliations

Institute of Molecular Biology, University of Zurich, CH-8057 Zurich, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12360578

Citation

Dong, Zhizhong, et al. "Overexpression of Parkinson's Disease-associated alpha-synucleinA53T By Recombinant Adeno-associated Virus in Mice Does Not Increase the Vulnerability of Dopaminergic Neurons to MPTP." Journal of Neurobiology, vol. 53, no. 1, 2002, pp. 1-10.
Dong Z, Ferger B, Feldon J, et al. Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP. J Neurobiol. 2002;53(1):1-10.
Dong, Z., Ferger, B., Feldon, J., & Büeler, H. (2002). Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP. Journal of Neurobiology, 53(1), 1-10.
Dong Z, et al. Overexpression of Parkinson's Disease-associated alpha-synucleinA53T By Recombinant Adeno-associated Virus in Mice Does Not Increase the Vulnerability of Dopaminergic Neurons to MPTP. J Neurobiol. 2002;53(1):1-10. PubMed PMID: 12360578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of Parkinson's disease-associated alpha-synucleinA53T by recombinant adeno-associated virus in mice does not increase the vulnerability of dopaminergic neurons to MPTP. AU - Dong,Zhizhong, AU - Ferger,Boris, AU - Feldon,Joram, AU - Büeler,Hansruedi, PY - 2002/10/3/pubmed PY - 2002/11/26/medline PY - 2002/10/3/entrez SP - 1 EP - 10 JF - Journal of neurobiology JO - J Neurobiol VL - 53 IS - 1 N2 - Mutations in the alpha-synuclein gene are linked to a rare dominant form of familial Parkinson's disease, and alpha-synuclein is aggregated in Lewy bodies of both sporadic and dominant Parkinson's disease. It has been proposed that mutated alpha-synuclein causes dopaminergic neuron loss by enhancing the vulnerability of these neurons to a variety of insults, including oxidative stress, apoptotic stimuli, and selective dopaminergic neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To test this hypothesis in vivo, we overexpressed human alpha-synuclein(A53T) in the substantia nigra of normal and MPTP-treated mice by rAAV-mediated gene transfer. Determination of dopaminergic neuron survival, striatal tyrosine hydroxylase fiber density, and striatal content of dopamine and its metabolites in rAAV-injected and uninjected hemispheres demonstrated that alpha-synuclein(A53T) does not increase the susceptibility of dopaminergic neurons to MPTP. Our findings argue against a direct detrimental role for (mutant) alpha-synuclein in oxidative stress and/or apoptotic pathways triggered by MPTP, but do not rule out the possibility that alpha-synuclein aggregation in neurons exposed to oxidative stress for long periods of time may be neurotoxic. SN - 0022-3034 UR - https://www.unboundmedicine.com/medline/citation/12360578/Overexpression_of_Parkinson's_disease_associated_alpha_synucleinA53T_by_recombinant_adeno_associated_virus_in_mice_does_not_increase_the_vulnerability_of_dopaminergic_neurons_to_MPTP_ L2 - https://doi.org/10.1002/neu.10094 DB - PRIME DP - Unbound Medicine ER -