Dopamine Transporter/α-Synuclein Complexes Are Altered in the Post Mortem Caudate Putamen of Parkinson's Disease: An In Situ Proximity Ligation Assay Study

International Journal of Molecular Sciences
Francesca LonghenaArianna Bellucci

Abstract

Parkinson's disease (PD) is characterized by the degeneration of the dopaminergic nigrostriatal neurons and the presence of Lewy bodies (LB) and Lewy neurites (LN) mainly composed of α-synuclein. By using the in situ proximity ligation assay (PLA), which allows for the visualization of protein-protein interactions in tissues to detect dopamine transporter (DAT)/α-synuclein complexes, we previously described that these are markedly redistributed in the striatum of human α-synuclein transgenic mice at the phenotypic stage, showing dopamine (DA) release impairment without a DAT drop and motor symptoms. Here, we used the in situ PLA to investigate DAT/α-synuclein complexes in the caudate putamen of PD patients and age-matched controls. They were found to be redistributed and showed an increased size in PD patients, where we observed several neuropil-like and neuritic-like PLA-positive structures. In the PD brains, DAT immunolabeling showed a pattern similar to that of in situ PLA in areas with abundant α-synuclein neuropathology. This notwithstanding, the in situ PLA signal was only partially retracing DAT or α-synuclein immunolabeling, suggesting that a large amount of complexes may have been lost along with the degeneration proce...Continue Reading

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Citations

Jul 14, 2020·Frontiers in Neuroscience·Qiao MaoXingguang Luo
Jul 26, 2019·International Journal of Molecular Sciences·Víctor Fernández-DueñasFrancisco Ciruela
Jun 27, 2018·Journal of Neural Transmission·Kurt A Jellinger
Oct 4, 2019·Brain : a Journal of Neurology·Yaping ChuJeffrey H Kordower
Jun 19, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Junpei KobayashiMasashi Aoki
Jan 6, 2019·International Journal of Molecular Sciences·Francesca LonghenaArianna Bellucci
Mar 7, 2021·NPJ Parkinson's Disease·Mengfei BuHabibeh Khoshbouei
Apr 8, 2021·Journal of Experimental Pharmacology·Thomas Müller
Jan 18, 2022·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gaia FaustiniArianna Bellucci

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Methods Mentioned

BETA
transgenic
proximity ligation assay

Software Mentioned

Adobe Photoshop CC

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