Importancia de los sistemas de reciclaje celular en células procedentes de enfermos de Parkinson

Résumé

Autophagy, for the greek “self eating”, is a cell mechanism responsible for degradation of cell components in order to maintain their homeostasis, however, it is commonly altered and compromised in several diseases, including neurodegenerative ones. These illnesses are growing importance because of the increase of the life span and time exposure to agents that may influence their progression. Thus, in such diseases with a multifactorial ethiology, any information that may mitigate or reduce their symptoms will be the key in establishing proper ways to face their progression. Parkinson´s disease (PD) can be considered as a multifactorial disease as environment, genetic factors and aging are involved. Within genetic factors, there is 23 gens involved in PD pathiology. Among them, LRRK2 protein and their mutations, inherited in an autosomal dominant manner, are responsible of most of genetic PD cases. In our lab, a relationship between G2019S LRRK2 mutation and an upregulation of macroautophagy that compromises cell viability has already been established. R1441G LRRK2 mutation is highly frequent in Basque Country, and, after G2019S, is the most important in PD pathogenesis. This doctoral dissertation aims to characterize whether this mutation affects autophagy mechanism in R1441G LRRK2 human fibroblasts obtained from PD patients in physiological conditions as well as in inhibition or induction of this mechanism.