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Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains.
Brain Pathol. 2018 Nov; 28(6):875-888.BP

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.

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Authors+Show Affiliations

Longhena F
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Faustini G
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Varanita T
Department of Biology, University of Padova, Padova, Italy.
Zaltieri M
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Porrini V
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Tessari I
Department of Biology, University of Padova, Padova, Italy.
Poliani PL
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Missale C
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Borroni B
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Padovani A
Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Bubacco L
Department of Biology, University of Padova, Padova, Italy.
Pizzi M
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Spano P
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. IRCCS San Camillo Hospital for Neurorehabilitation (NHS-Italy), Venice Lido, Italy.
Bellucci A
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Laboratory of Personalized and Preventive Medicine, University of Brescia, Brescia, Italy.

MeSH

AgedAged, 80 and overAnimalsDopamineHippocampusHumansLewy BodiesMiceMice, Inbred C57BLMice, KnockoutParkinson DiseasePutamenSubstantia NigraSynapsinsalpha-Synuclein

Pub Type(s)

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

Language

eng

PubMed ID

29330884

Citation

Longhena, Francesca, et al. "Synapsin III Is a Key Component of Α-synuclein Fibrils in Lewy Bodies of PD Brains." Brain Pathology (Zurich, Switzerland), vol. 28, no. 6, 2018, pp. 875-888.
Longhena F, Faustini G, Varanita T, et al. Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains. Brain Pathol. 2018;28(6):875-888.
Longhena, F., Faustini, G., Varanita, T., Zaltieri, M., Porrini, V., Tessari, I., Poliani, P. L., Missale, C., Borroni, B., Padovani, A., Bubacco, L., Pizzi, M., Spano, P., & Bellucci, A. (2018). Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains. Brain Pathology (Zurich, Switzerland), 28(6), 875-888. https://doi.org/10.1111/bpa.12587
Longhena F, et al. Synapsin III Is a Key Component of Α-synuclein Fibrils in Lewy Bodies of PD Brains. Brain Pathol. 2018;28(6):875-888. PubMed PMID: 29330884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synapsin III is a key component of α-synuclein fibrils in Lewy bodies of PD brains. AU - Longhena,Francesca, AU - Faustini,Gaia, AU - Varanita,Tatiana, AU - Zaltieri,Michela, AU - Porrini,Vanessa, AU - Tessari,Isabella, AU - Poliani,Pietro Luigi, AU - Missale,Cristina, AU - Borroni,Barbara, AU - Padovani,Alessandro, AU - Bubacco,Luigi, AU - Pizzi,Marina, AU - Spano,PierFranco, AU - Bellucci,Arianna, Y1 - 2018/02/23/ PY - 2017/7/20/received PY - 2017/12/21/accepted PY - 2018/1/14/pubmed PY - 2019/5/29/medline PY - 2018/1/14/entrez KW - Lewy bodies KW - Lewy body dementia KW - Parkinson's disease KW - synapsin III KW - α-synuclein SP - 875 EP - 888 JF - Brain pathology (Zurich, Switzerland) JO - Brain Pathol VL - 28 IS - 6 N2 - 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. SN - 1750-3639 UR - https://www.unboundmedicine.com/medline/citation/29330884/Synapsin_III_is_a_key_component_of_α_synuclein_fibrils_in_Lewy_bodies_of_PD_brains_ DB - PRIME DP - Unbound Medicine ER -