Reference:
3
Abstract:
This study aims at understanding the causes and the ways that lead to the failure of small structures, dendritic spines, distributed on neurons in regions (synapses) in which nerve cells are approaching to communicate with each other. Rett Syndrome In this malfunction has a reversible and an irreversible phase . Specifically, the objective of this research is to analyze the relationship of specific groups of molecules, the alteration in the absence of MeCP2, the genetic cause of Rett syndrome, would be responsible for the transition between the reversible and the irreversible stage. This could allow us to block the progression from reversible to the irreversible phase of the disease . Recent experiments with animal models have shown how the main nerve cells, neurons, and in particular specific structures of these cells, called “dendritic spines”, localized in level of the region in which neurons come into contact with each other to communicate (forming structures called synapses), are able to change hand in hand that the individual learns and lives of the experiences, the phenomenon known as neuronal plasticity. At the base of the processes of learning, memory and normal functioning of the human brain is the ability of these structures, the dendritic spines, to respond and adapt to external stimuli. analysis of animal models available to study Rett syndrome has indicated that altered levels of MeCP2 produce major changes in the nerve cells of the brain. Rett in mice show defects in neuronal morphology of dendritic spines, as well as alterations in synaptic transmission and plasticity, in other words the thorns appear less mobile and not functioning ( Landi et al, 2011). Thus, according to the latest findings, the lack of MeCP2 might have as a first symptom of pathological ‘alteration in the formation of these special structures in a very early stage of the disease. There is experimental evidence that in neurodegenerative diseases, the most common and therefore most studied, the dysfunction of synapses appears as a dynamic process, with an initial phase during which the reversible synaptic function decreases, to progress, subsequently, to an irreversible stage that leads to death of synaptic contact between neurons. We want to analyze the synapses of neurons of mice and Rett’s see if we can stop or slow the cognitive decline that occurs in the disease. study we propose has as its objective the understanding of the causes and the ways that lead to the degeneration of the spine in a mouse model Rett missing the MeCP2 protein. In particular we want to study in these mice dysfunction of synapses and discover the molecular cascades that govern this first mechanism, correlating with Rett syndrome. In particular, we will analyze the activation of intracellular signal transduction and the presence of alterations in the expression of specific genes and protein synthesis, to identify the pathological processes involved therefore in the mechanisms that lead to the development of the disease. Knowledge of processes that occur within neurons sick and the molecules involved in synaptic dysfunction would block the progression of the degeneration of synapses and pave the way for such therapeutic applications. There is experimental evidence that in neurodegenerative diseases, the most common and therefore more studied, the dysfunction of synapses appears as a dynamic process, with an initial phase during which the reversible synaptic function decreases, to progress, subsequently, to an irreversible stage that leads to death of synaptic contact between neurons. We want to analyze the synapses of neurons of mice and Rett’s see if we can stop or slow the cognitive decline that occurs in the disease. study we propose has as its objective the understanding of the causes and the ways that lead to the degeneration of the spine in a mouse model Rett missing the MeCP2 protein. In particular we want to study in these mice dysfunction of synapses and discover the molecular cascades that govern this first mechanism, correlating with Rett syndrome. In particular, we will analyze the activation of intracellular signal transduction and the presence of alterations in the expression of specific genes and protein synthesis, to identify the pathological processes involved therefore in the mechanisms that lead to the development of the disease. Knowledge of processes that occur within neurons sick and the molecules involved in synaptic dysfunction would block the progression of the degeneration of synapses and pave the way for such therapeutic applications. therefore propose to study the early events synaptic dysfunction in the brains of mice with Rett methods of biochemistry, molecular biology and genetics in order to determine a correlation between the onset of synaptic malfunction and the two proteins JNK and MeCP2. Finally, if it is demonstrated in Rett syndrome l ‘importance of JNK in the pathogenesis of the disease, will be studied the effect of D-JNKI1 (Mario Negri) in preclinical studies to test the ability to prevent the loss of synapses in mice and Rett block the symptoms of the disease.
PROJECT DETAILS
beginning: 2012.
end: 2013.
Country of research: Italy
Counry of funding source: Italy
Funding organization: AIRETT
Financing: PRIVATE FUNDERS – 100 000 €