Neuroscience
Neuropsychopharmacology
The main topics of Valtorta’s lab research activity relate to the study of the molecular mechanisms underlying the processes of neuronal development and synaptic function, with emphasis on membrane trafficking, cytoskeletal dynamics and protein phosphorylation events. The recognition that synapse dysfunction is a major determinant of many neurological and psychiatric diseases has led to the concept of synaptopathies.
Research activity
The group has applied its extensive experience in the study of synapse development and function to the study of the molecular mechanisms underlying various synaptopathies. The long-term goal of this project is to decipher the molecular mechanisms through which mutations in genes coding proteins involved in neuronal membrane trafficking lead to neurological disorders, with an emphasis on epilepsy, mental retardation and autism spectrum disorders. Since it is now accepted that impairment of synaptic function is an early event also in diseases previously thought to be essentially neurodegenerative (e.g. Parkinson disease) or neuroinflammatory (e.g. multiple sclerosis), the unit is extending their research also to these disorders. They believe that a better understanding of synaptic physiology and of its alteration in synaptopathies may drive a transition from a disease classification based on phenomenology to one based on pathophysiological underpinnings. Such a shift will offer novel clues for the development of therapeutic strategies.
Guarnieri FC, Pozzi D, Raimondi A, Fesce R, Valente MM, Delvecchio VS, Van Esch H, Matteoli M, Benfenati F, D’Adamo P, Valtorta F. A novel SYN1 missense mutation in nonsyndromic X-linked intellectual disability affects synaptic vesicle life cycle, clustering and mobility. Human Molecular Genetics 2017 Dec 1;26(23):4699-4714.
Sassone J, Serratto GM, Passafaro M, Valtorta F, Ciammola A. The synaptic function of parkin. Brain 2017 Sep 1;140(9):2265-2272.
Valtorta F, Benfenati F, Zara F, Meldolesi J. PRRT2: from paroxysmal disorders to regulation of synaptic function. Trends in Neurosciences 2016 Oct;39(10):668-679.
Valente P, Castroflorio E, Rossi P, Fadda M, Sterlini B, Cervigni RI, Prestigio C, Giovedì S, Onofri F, Mura E, Guarnieri F, Orlando M, Zara F, Fassio A, Valtorta F, Baldelli P, Corradi A, Benfenati F. PRRT2 is a key component of the Ca2+-dependent release machinery. Cell Reports, 15: 117-131, 2016
Bellani S, Mescola A, Ronzitti G, Tsushima H, Tilve S, Canale C, Valtorta F, Chieregatti E. GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein. Cell Death and Differentiation 2014 Dec;21(12):1971-83.
Fornasiero F, Raimondi A, Guarnieri F, Fesce R, Benfenati F, Valtorta F. Synapsins contribute to the dynamic spatial organization of synaptic vesicles in an activity-dependent manner. Journal of Neuroscience 2012 Aug 29;32(35):12214-27.
Gärtner A, Fornasiero EF, Munck S, Vennekens K, Seuntjens E, Huttne WB, Valtorta F, Dotti CG. N-Cadherin specifies first asymmetry in developing pyramidal neurons. EMBO Journal 2012 Apr 18;31(8):1893-903.
Valtorta F, Meldolesi J, Fesce R. Synaptic vesicles: is kissing a matter of competence? Trends in Cell Biology 2001 Aug;11(8):324-8.
Greengard P, Valtorta F, A.J. Czernik AJ, Benfenati F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 1993 Feb 5;259(5096):780-5.
Torri Tarelli F, M. Bossi M, R. Fesce R, P. Greengard P, Valtorta F. Synapsin I partially dissociates from synaptic vesicles during exocytosis induced by electrical stimulation. Neuron. 1992 Dec;9(6):1143-53.
