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Eps8
15/02/2019

EPS8-A NEW ITALIAN CONTRIBUTION TO THE UNDERSTANDING OF GENETIC MECHANISMS UNDERLYING NEURODEVELOPMENTAL DISORDERS

The neuron, like all cells of the human body, is characterized by a dense network of fibrous proteins comprising the cytoskeleton. This determines the gelatinous consistency of the cytoplasm and the ordered arrangement of the organelles contained in it. In recent years, the filaments that constitute the cytoskeleton, especially microtubules and actin, have proved increasingly of fundamental importance in the genesis of synapses, or of conjunctions between cells, and thus in the brain functions of the base. Indeed synaptic plasticity, the process through which the human brain is continuously reshaped on the basis of the change of environmental stimuli, is decisive for the learning, for the development and maintenance of memory. Studies on various neurological disorders have repeatedly found a strong correlation between the shape and number of dendritic spines and synapses relative efficiency. In 2013 researchers at the Institute of Neuroscience CNR and Humanitas found that a protein called Eps8, is stored in the heads of dendritic spines during long-term strengthening cultural chemically induced and that inhibition of its activity by actin capping severely limits the expansion and plasticity of spines. Mice deprived of Eps8 show impairment of cognitive functions associated with neural spines immature and unable to respond to stimuli enhancement. Researchers at the Institute of Neuroscience CNR and Humanitas also found that the levels of Eps8 are significantly lower in the brains of people with autism or intellectual disability carriers than people in the general population. The communication between nerve cells is vital in the functioning of the brain - says Michela Matteoli, who led the study together with Elisabetta Menna. Synapses are the structures that mediate the transfer of information between neurons and are highly dynamic, varying in number and shape during brain development and subsequent changes in the whole of life. In 2017 Hsu and collaborators, at the Department of Pharmacology of the College of Medicine of the National Cheng Kung University, Taiwan demonstrated that in mice a genetic deletion of Eps8 from excitatory neurons leads to impaired performance in a novel object recognition test. These was associated with an hyperfunction of N-methyl-d-aspartate receptors in the cognitive deficits and with a novel role for Eps8 in regulating hippocampal long-term synaptic plasticity and cognitive functions.

 

REFERENCES

Menna E, Zambetti S, Morini R, Donzelli A, Disanza A, Calvigioni D, Braida D, Nicolini C, Orlando M, Fossati G, Cristina Regondi M, Pattini L, Frassoni C, Francolini M, Scita G, Sala M, Fahnestock M, Matteoli M. Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity. EMBO J. 2013 May 17. doi: 10.1038/emboj.2013.107.

Wang YT, Huang CC, Lin YS, Huang WF, Yang CY, Lee CC, Yeh CM, Hsu KS. Conditional deletion of Eps8 reduces hippocampal synaptic plasticity and impairs cognitive function. Neuropharmacology. 2017 Jan; 112(A): 113-123.

Marco O. Bertelli