Project: LOss of neurotrophic factors in neurodegenerative DEmentias: Back to the crossroads of proteins

Acronym	LODE (Reference Number: PATHWAYS-200-059)
Project Topic	The recognition that non-monogenic as well monogenic forms of dementia result substantially in the same disease, suggests that fundamental, simple mechanisms may underlie the apparent complexity of observed human neurodegenerative disorders. This project explores a key common pathological mechanism across AD, FTD, LBD. During conditions characterized by progressive loss of neurons, exosomes could become the key player of neuronal communication and the crossroads of proteins: accordingly, survival of neurons could be easily affected by factors modulating exosomes release and/or composition. Our working hypothesis is that loss of trophic factors is one of the main determinants affecting exosome release, thus influencing the fate of disease-related proteins across dementias. We envisage to address this issue by testing the link between i) neurotrophic factors and exosome generation (cellular and animal studies; neurobiological and neuropathological studies on patients); ii) exosome generation and neurodegeneration (cellular and animal studies; neurobiological, neuropathological and genetic studies on patients). To achieve these goals, we have organized a multidisciplinary team with a proven expertise in studying i) AD, FTD, LBD; ii) cellular and animal models; iii) human brain (neuropathology) and circulating disease markers; iv) proteins aggregation (abeta, tau, alpha-synuclein) v) exosome isolation/characterization; vi) genetic disease determinants; vii) nanoparticle delivery systems. LODE will achieve a great gain of knowledge regarding mechanisms of neurodegeneration but may also unmask novel disease markers and provide new targets for putative therapeutic intervention. Gender will be taken into account both in collecting and analysing data.
Network	JPco-fuND
Call	A CALL FOR MULTINATIONAL RESEARCH PROJECTS FOR PATHWAY ANALYSIS ACROSS NEURODEGENERATIVE DISEASES

Project partner

Number	Name	Role	Country
1	PROVINCIA LOMBARDO VENETA ORDINE OSPEDALIERO DI SAN GIOVANNI DI DIO FATEBENEFRATELLI	Coordinator	Italy
2	FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA	Partner	Italy
3	University of Cambridge	Partner	United Kingdom
4	MAX-PLANCK-GESELLSCHAFT	Partner	Germany