Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K-resistant neuropathological inclusions that contained both α-syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α-syn-positive fibrils in LB-enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α-syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α-syn interactant and a key component of LB fibrils in the brain of patients affected by PD

Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains / Longhena, Francesca; Faustini, Gaia; Varanita, Tatiana; Zaltieri, Michela; Porrini, Vanessa; Tessari, Isabella; Poliani, PIETRO LUIGI; Missale, Cristina; Borroni, Barbara; Padovani, Alessandro; Bubacco, Luigi; Pizzi, Marina; Spano, Pierfranco; Bellucci, Arianna. - In: BRAIN PATHOLOGY. - ISSN 1015-6305. - 28:6(2018), pp. 875-888. [10.1111/bpa.12587]

Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains

Poliani Pietro Luigi;
2018-01-01

Abstract

Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of α-synuclein (α-syn), are neuropathological hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal phosphoprotein synapsin III (syn III) controls dopamine release via cooperation with α-syn and modulates α-syn aggregation. Here, we observed that LB and LN, in the substantia nigra of PD patients and hippocampus of one subject with DLB, displayed a marked immunopositivity for syn III. The in situ proximity ligation assay revealed the accumulation of numerous proteinase K-resistant neuropathological inclusions that contained both α-syn and syn III in tight association in the brain of affected subjects. Most strikingly, syn III was identified as a component of α-syn-positive fibrils in LB-enriched protein extracts from PD brains. Finally, a positive correlation between syn III and α-syn levels was detected in the caudate putamen of PD subjects. Collectively, these findings indicate that syn III is a crucial α-syn interactant and a key component of LB fibrils in the brain of patients affected by PD
2018
Lewy bodies
Lewy body dementia
Parkinson’s disease
alpha-synuclein
synapsin III
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/162422
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