Elisa Greggio

The Greggio Lab is interested in studying the molecular mechanisms underlying the early events associated with neurodegenerative diseases. To this aim, we combine cellular and mouse models of genetic forms of Parkinson’s disease (PD) and Hereditary Spastic Paraplegia (HSP) to investigate the impact of gain and loss of function mutations on neuronal and glia cells homeostasis. The final goal is to translate the mechanistic knowledge gained from these models into novel pathways that can be targeted in the clinics.

Currently ongoing projects aim to dissect:  1) the molecular mechanisms underlying peripheral and central inflammation in Parkinson’s disease using mutant LRRK2 as a model of disease; 2) the role of the kinase LRRK2 at the synapse and the impact of brain derived neurotrophic factors on striatal postsynaptic function; 3) the impact of the kinase PAK6 on LRRK2 activity and its role in brain ciliogenesis; 4) novel mechanisms regulating SPG11 trafficking and the impact of SPG11 loss of function in HSP models.

Iannotta L, Greggio E^CA. LRRK2 signaling in neurodegeneration: two decades of progress. Essays Biochem. 2021 Dec 13:EBC20210013. doi: 10.1042/EBC20210013.

Pischedda F, Cirnaru MD, Ponzoni L, Sandre M, Biosa A, Carrion MP, Marin O, Morari M, Pan L, Greggio E, Bandopadhyay R, Sala M, Piccoli G. LRRK2 G2019S kinase activity triggers neurotoxic NSF aggregation. Brain. 2021 Jun 22;144(5):1509-1525. doi: 10.1093/brain/awab073.

Iannotta L, Biosa A, Kluss JH, Tombesi G, Kaganovich A, Cogo S, Plotegher N, Civiero L, Lobbestael E, Baekelandt V, Cookson MR, Greggio E^CA. Divergent Effects of G2019S and R1441C LRRK2 Mutations on LRRK2 and Rab10 Phosphorylations in Mouse Tissues. Cells. 2020 Oct 22;9(11):2344. doi: 10.3390/cells9112344.

Russo I, Kaganovich A, Ding J, Landeck N, Mamais A, Varanita T, Biosa A, Tessari I, Bubacco L, Greggio E^CA, Cookson MR^CA. Transcriptome analysis of LRRK2 knock-out microglia cells reveals alterations of inflammatory- and oxidative stress-related pathways upon treatment with α-synuclein fibrils. Neurobiol Dis. 2019 Sep;129:67-78. doi: 10.1016/j.nbd.2019.05.012.

Russo I, Di Benedetto G, Kaganovich A, Ding J, Mercatelli D, Morari M, Cookson MR, Bubacco L, Greggio E. Leucine-rich repeat kinase 2 controls protein kinase A activation state through phosphodiesterase 4. J Neuroinflammation. 2018 Oct 27;15(1):297. doi: 10.1186/s12974-018-1337-8.

Civiero L, Cogo S, Kiekens A, Morganti C, Tessari I, Lobbestael E, Baekelandt V, Taymans JM, Chartier-Harlin MC, Franchin C, Arrigoni G, Lewis PA, Piccoli G, Bubacco L, Cookson MR, Pinton P,  Greggio E^CA. PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2. Front Mol Neurosci. 2017 Dec 14;10:417. doi: 10.3389/fnmol.2017.00417.

Russo I, Berti G, Plotegher N, Bernardo G, Filograna R, Bubacco L,  Greggio E^CA. Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells. J Neuroinflammation. 2015 Dec 9;12:230. doi: 10.1186/s12974-015-0449-7

Belluzzi E, Gonnelli A, Cirnaru MD, Marte A, Plotegher N, Russo I, Civiero L, Cogo S, Carrion MP, Franchin C, Arrigoni G, Beltramini M, Bubacco L, Onofri F, Piccoli G,  Greggio E^CA. LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate. Mol Neurodegener. 2016 Jan 13;11:1. doi: 10.1186/s13024-015-0066-z.

Civiero L, Cirnaru MD, Beilina A, Rodella U, Russo I, Belluzzi E, Lobbestael E, Reyniers L, Hondhamuni G, Lewis PA, Van den Haute C, Baekelandt V, Bandopadhyay R, Bubacco L, Piccoli G, Cookson MR, Taymans JM,  Greggio E^CA. Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain. J Neurochem. 2015 Dec;135(6):1242-56. doi: 10.1111/jnc.13369.

Beilina A, Rudenko IN, Kaganovich A, Civiero L, Chau H, Kalia SK, Kalia LV, Lobbestael E, Chia R, Ndukwe K, Ding J, Nalls MA; International Parkinson’s Disease Genomics Consortium; North American Brain Expression Consortium, Olszewski M, Hauser DN, Kumaran R, Lozano AM, Baekelandt V, Greene LE, Taymans JM, Greggio E, Cookson MR. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc Natl Acad Sci U S A. 2014 Feb 18;111(7):2626-31. doi: 10.1073/pnas.1318306111.