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Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease.
J Neurochem. 2004 Oct; 91(2):451-61.JN

Abstract

To elucidate the role of alpha-synuclein in the pathogenesis of Parkinson's disease, both human alpha-synuclein transgenic mice and targeted overexpression of human alpha-synuclein in rat substantia nigra using viral vector-based methods have been studied, however, little is known about the pathogenetic changes of dopaminergic neuron loss. Therefore, it is necessary to address whether the pathogenetic changes in brains with Parkinson's disease are recapitulated in these models. Here, we used the recombinant adeno-associated viral (rAAV) vector system for human alpha-synuclein gene transfer to rat substantia nigra and observed approximately 50% loss of dopaminergic neurons at 13 weeks after infection, which was comparably slower than the progression of neurodegeneration reported in other studies. In the slower progression of neurodegeneration, we identified several important features in common with the pathogenesis of Parkinson's disease, such as phosphorylation of alpha-synuclein at Ser129 and activation of caspase-9. Both findings were also evident in cortical tissues overexpressing alpha-synuclein via rAAV. Our results indicate that overexpression of alpha-synuclein via rAAV apparently recapitulates several important features of brains with Parkinson's disease and dementia with Lewy bodies, and thus alpha-synucleinopathy described here is likely to be an ideal model for the study of the pathogenesis of Parkinson's disease and dementia with Lewy bodies.

Authors+Show Affiliations

Research Institute for Diseases of Old Age, Juntendo University, Bunkyo, Tokyo, Japan.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

15447678

Citation

Yamada, Masanori, et al. "Overexpression of Alpha-synuclein in Rat Substantia Nigra Results in Loss of Dopaminergic Neurons, Phosphorylation of Alpha-synuclein and Activation of Caspase-9: Resemblance to Pathogenetic Changes in Parkinson's Disease." Journal of Neurochemistry, vol. 91, no. 2, 2004, pp. 451-61.
Yamada M, Iwatsubo T, Mizuno Y, et al. Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. J Neurochem. 2004;91(2):451-61.
Yamada, M., Iwatsubo, T., Mizuno, Y., & Mochizuki, H. (2004). Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. Journal of Neurochemistry, 91(2), 451-61.
Yamada M, et al. Overexpression of Alpha-synuclein in Rat Substantia Nigra Results in Loss of Dopaminergic Neurons, Phosphorylation of Alpha-synuclein and Activation of Caspase-9: Resemblance to Pathogenetic Changes in Parkinson's Disease. J Neurochem. 2004;91(2):451-61. PubMed PMID: 15447678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. AU - Yamada,Masanori, AU - Iwatsubo,Takeshi, AU - Mizuno,Yoshikuni, AU - Mochizuki,Hideki, PY - 2004/9/28/pubmed PY - 2004/11/16/medline PY - 2004/9/28/entrez SP - 451 EP - 61 JF - Journal of neurochemistry JO - J Neurochem VL - 91 IS - 2 N2 - To elucidate the role of alpha-synuclein in the pathogenesis of Parkinson's disease, both human alpha-synuclein transgenic mice and targeted overexpression of human alpha-synuclein in rat substantia nigra using viral vector-based methods have been studied, however, little is known about the pathogenetic changes of dopaminergic neuron loss. Therefore, it is necessary to address whether the pathogenetic changes in brains with Parkinson's disease are recapitulated in these models. Here, we used the recombinant adeno-associated viral (rAAV) vector system for human alpha-synuclein gene transfer to rat substantia nigra and observed approximately 50% loss of dopaminergic neurons at 13 weeks after infection, which was comparably slower than the progression of neurodegeneration reported in other studies. In the slower progression of neurodegeneration, we identified several important features in common with the pathogenesis of Parkinson's disease, such as phosphorylation of alpha-synuclein at Ser129 and activation of caspase-9. Both findings were also evident in cortical tissues overexpressing alpha-synuclein via rAAV. Our results indicate that overexpression of alpha-synuclein via rAAV apparently recapitulates several important features of brains with Parkinson's disease and dementia with Lewy bodies, and thus alpha-synucleinopathy described here is likely to be an ideal model for the study of the pathogenesis of Parkinson's disease and dementia with Lewy bodies. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15447678/Overexpression_of_alpha_synuclein_in_rat_substantia_nigra_results_in_loss_of_dopaminergic_neurons_phosphorylation_of_alpha_synuclein_and_activation_of_caspase_9:_resemblance_to_pathogenetic_changes_in_Parkinson's_disease_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2004&volume=91&issue=2&spage=451 DB - PRIME DP - Unbound Medicine ER -