Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T a-synuclein mutation Huang, Yue Chegini, Fariba Chua, Germaine Murphy, Karen Gai, Wei Ping Halliday, Glenda M 2013-04-03T23:00:51Z 2013-04-03T23:00:51Z 2012-01-13
dc.description.abstract The A53T mutation in the a-synuclein gene causes autosomal-dominant Lewy body Parkinson’s disease (PD). Cultured cell models have linked this mutation to increased cell macroautophagy, although evidence of enhanced macroautophagy in patients with this mutation has not been assessed. Objective: To determine whether macroautophagy is increased by the A53T a-synuclein gene mutation in PD patients and cell models. Methods: Formalin-fixed paraffin-embedded 10 μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T a-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain Bank. Lewy bodies were isolated from frontal cortex of a case with late stage PD (recruited from South Australian Brain Bank). Immunohistochemistry was performed for a-synuclein and the macroautophagy markers autophagy-specific gene (ATG) 5, ATG6/Beclin1 and ATG8/LC3. SHSY5Y cells were transfected with wild type or A53T mutant a-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western blotting. Results: a-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients, and perinuclear cytoplasmic a-synuclein aggregates were observed in the a-synuclein A53T gene transfected SH-SY5Y cells compared to wild type transfections. All PD patients (with or without A53T mutations) had increased immunohistochemical evidence for macroautophagy compared with controls, and the levels of the ATG5 complex were equally increased in wild type and A53T a-synuclein gene transfected cells compared to controls. Conclusion: Despite increased a-synuclein accumulation with A53T mutations, macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type a-synuclein, suggesting that mutated a-synuclein protein is not removed by macroautophagy. en
dc.identifier.citation Huang, Y., Chegini, F., Chua, G., Murphy, K., Gai, W. and Halliday, G.M., 2012. Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T a-synuclein mutation. Translational Neurodegeneration, 1:2. en
dc.identifier.doi en
dc.identifier.issn 2047-9158
dc.language.iso en
dc.oaire.license.condition.license CC-BY
dc.publisher BioMed Central Ltd. en
dc.relation en
dc.relation.grantnumber NHMRC/510186 en
dc.relation.grantnumber NHMRC/535014 en
dc.rights Copyright © 2012 Huang et al.; licensee BioMed Central Ltd. en
dc.rights.holder Huang et al.; licensee BioMed Central Ltd. en
dc.subject Neuroscience en
dc.subject Parkinson's disease en
dc.subject Macroautophagy en
dc.subject Alpha-synuclein en
dc.title Macroautophagy in sporadic and the genetic form of Parkinson’s disease with the A53T a-synuclein mutation en
dc.type Article en
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