Fasano, Dominga (2017) Exploring the role of Fig4 and Synj1 in the membrane trafficking and neurodegenaration in Charcot Marie Tooth 4J and Parkinson neuropathies. [Tesi di dottorato]

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Abstract

Homeostasis of eukaryotic cells is largely dependent on dynamic compartmentalization of the endo-membrane system. The membrane trafficking linking different organelles is essential to maintain a proper composition of various compartments as well as to transport various molecules to appropriate compartments. Thus, the molecular machinery regulating properly the intracellular membrane trafficking has a key role in the maintenance of organelle functionality and cell viability. It is not surprising that alterations in membrane trafficking can result in different pathologies. Respect to other cell types nervous system is more sensitive to disturbances of the membrane trafficking. Hence, to understand how alterations of the intracellular trafficking could lead to neurodegeneration, we focused our attention on two nervous system disorders, Charcot-Marie Tooth disease 4J (CMT4J) and Parkinson disease (PD), both caused by mutations of an inositol phospahatase (Fig4 and Synj1, respectively). Together with specific kinases, the activity of phospahatases control, the levels of phosphoinosities (PI), a class of phospholipids that even more is emerging to be involved in the regulation of membrane trafficking. Numerous findings highlighted that the levels of PI might be finely regulated, in time and in the space, and are critical for membrane homeostasis. Specifically PI metabolism seems critical for nervous system functions. Aim of my PhD project was to explore the role of Fig4 and Synj1 in the membrane trafficking and neurodegenaration in CMT4J and Parkinson neuropathies.

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