Alteration of endosomal trafficking is associated with neurodegenerative diseases

Homeostasis of eukaryotic cells is largely dependent on dynamic com-partmentalization of the endo-membrane system. The membrane traf-ficking linking different organelles is essential to maintain a proper composition of various compartments as well as to transport various molecules to appropriate compartments. Respect to other cell types nervous system is more sensitive to alterations of the membrane traf-ficking. In the last years, we studied the role of endosomal trafficking in neurodegeneration focusing on two nervous system disorders, Charcot-Marie Tooth disease 4 J (CMT4 J) and a new form of autosomal recessive early-onset parkinsonism (PARK20), both caused by muta-tions of an inositol phosphatase (Fig 4 and Synj1, respectively). Our recent investigations show that:1. Synj1 plays a crucial role in regulating the homeostasis and func-tions of early endosomal compartments in different cell types and in fibroblasts of PARK20 patients;2. the loss of Fig 4 drastically alters the whole endo-lysosome axis (lysosomes, but also late and early endosomes result enlarged and more numerous) implying its essential role for the homeostasis and function of these compartments.All together, our data provide evidence for the implication of endo-somal pathway in neurodegeneration, emphasising the link between endosomal trafficking and neurodegenerative diseases.