Proteostasis

…the lifespan, connecting fundamental proteostasis mechanisms with ageing and degenerative disease.

Dopaminergic neuron functions rely on active synaptic vesicle dynamics and proteostasis. Deficientendocytosis due to lack of endophilins-A, key endocytic adaptors, alters the expression of genesassociated with ataxia, Parkinson's disease and protein homeostasis. Fbxo32, a E3-ubiquitin ligaserequired for muscle atrophy but also expressed in the brain, was shown to be up-regulated inendophilin mutants. Hence, we aimed to investigate the dopaminergic system alterations in theendophilins-A murine model, and explore the effects of Fbxo32 genetic modifications on dopaminedegeneration in this mammali

…of ageing is the loss of proteostasis. Neddylation maintains proteome homeostasis, it is involved in neuronal differentiation and its deregulation is linked to neurodegenerative diseases. The role and mechanisms of Neddylation with physiological ageing remain still unclear.We studied the expression and impact of neddylation on ageing and cognitive decline. We found that neddylation increases with age in the hippocampus neurogenic niche both in human and mouse samples. Aged, but not young, Nae1+/- h

The development of human induced pluripotent stem cells (iPSC) and their subsequent differentiation into neurons has provided new opportunities for the generation of physiologically-relevant, in vitro disease models. I will present our work using iPSC to modal familial Alzheimer's Disease (fAD) and Frontotemporal Dementia (FTD). We have investigated the mutation-specific effects of APP and PSEN1 mutations on Abeta generation in neurons generated from individuals with fAD, revealing distinct mechanisms that may contribute to clinical heterogeneity in disease. I will also discuss our work to und

…to protein homeostasis, the so called proteostasis networks, have been identified in the pathogenesis of multiple neurodegenerative disorders and demonstrated to contribute to disease onset and progression. We are interested in autophagy, one of the components of the proteostasis network, and in the interplay of wo selective types of autophagy, chaperone-mediated autophagy (CMA) and endosomal microautophagy (eM