7 | Alpha-synuclein in the communication between perivascular macrophages and endothelial cells

Brain ischaemia leads to brain damage and disruption of the BBB, a process that is aggravated by α-synuclein. Several lines of evidence suggest that macrophages, including perivascular macrophages, release α-synuclein, which modulates BBB integrity. In this project we will investigate whether and how α-synuclein affects vascular homeostasis and macrophage activation/infiltration in physiology and brain ischaemia. Genetically modified cell and animal models, high-resolution intravital or 2-photon microscopy, molecular biology methods and viral vector-based techniques will be employed in this study.

Publications

• Porrini V, Mota M, Parrella E, Bellucci A, Benarese M, Faggi L, Tonin P, Spano P and Pizzi M. Mild inflammatory profile without gliosis in the c-Rel deficient mouse modeling a late-onset Parkinsonism. Front Aging Neurosci 2017;9:229.
• Kaminska B, Mota M, Pizzi M. Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation. Biochim Biophys Acta 2016;1862:339-351
• Porrini V, Lanzillotta A, Branca C, Benarese M, Parrella E, Lorenzini L, Calzà L, Flaibani R, Spano PF, Imbimbo BP, Pizzi M. CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience 2015;302:112-120
• Zaltieri M, Grigoletto J, Longhena F, Navarria L, Favero G, Castrezzati S, Colivicchi MA, Della Corte L, Rezzani R, Pizzi M, Benfenati F, Spillantini M G, Missale C, Spano PF, Bellucci A. α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons. J Cell Sci 2015;128:2231-2243.
• A Lanzillotta , G Pignataro , C Branca , O Cuomo, I Sarnico, M Benarese, L Annunziato, P Spano, M Pizzi. Targeted acetylation of NF-kappaB/RelA and histones by epigenetic drugs reduces post-ischemic brain injury in mice with an extended therapeutic window. Neurobiol Dis 2013;49:177-89.

Potential secondments

WWU (Lydia Sorokin), month 18-21.