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Guarnieri Fabrizia

Dettagli
Visite: 1524

guarnieriResearch scientist
c/o Università di Milano - Bicocca
Via Raoul Follereau, 3
20854 Vedano al Lambro
(MB)

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Autophagic regulation in neurons

Neurons are postmitotic cells that terminally differentiate early during development, have to survive for the entire life of the organism and cannot dilute damaged components by cell division. They are extremely polarised, and the distal proteome has to be continuously renewed. Given these peculiarities, neurons need a very efficient control of proteostasis and specialized quality control mechanisms. Autophagy, one of the main catabolic processes in a cell, is thus central for neuronal health and homeostasis.

Many neurodegenerative diseases are characterized by protein accumulations that cannot be efficiently eliminated and probably contribute to neuronal damage. Autophagic defects have been described in virtually all neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease. Quite invariably, the enhancement of autophagy in these conditions ameliorates protein deposition and disease symptoms in animal models.

Autophagy has also been implicated in axon outgrowth, synapse formation, synaptic plasticity and memory formation, and defective autophagy is starting to be recognized in neurodevelopmental disorders as well.

The study of neuronal autophagy has impressively expanded in the last ten year. Still, many basic and translational issues remain unsolved and represent my main research interest:

  • Are there neuron-specific (or neuronal subtype-specific) regulators of the autophagic pathway?
  • What are the signals that activate autophagy in neurons? Do they differ in the axonal vs somatodendritic compartment?
  • Why does brain autophagy lose its efficiency with ageing?
  • Can we monitor autophagic function in vivo?
  • Can we design drugs to specifically modulate neuronal autophagy in vivo?

 

Selected publications

Giovedì S, Ravanelli MM, Parisi B, Bettegazzi B, Guarnieri FC. Dysfunctional Autophagy and Endolysosomal System in Neurodegenerative Diseases: Relevance and Therapeutic Options.Front Cell Neurosci, 2020

Savino E, Cervigni RI, Povolo M, Stefanetti A, Ferrante D, Valente P, Corradi A, Benfenati F, Guarnieri FC*, Valtorta F*. Proline-rich transmembrane protein 2 (PRRT2) regulates the actin cytoskeleton during synaptogenesis. Cell Death Dis, 2020. *equal contribution

Piccini A, Castroflorio E, Valente P, Guarnieri FC, Aprile D, Michetti C, Bramini M, Giansante G, Pinto B, Savardi A, Cesca F, Bachi A, Cattaneo A, Wren JD, Fassio A, Valtorta F, Benfenati F, Giovedì S. APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell Reports, 2017

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 non-syndromic X-linked intellectual disability affects synaptic vesicle life cycle, clustering and mobility. Hum Mol Genet, 2017