The central theme of my research team concerns the molecular bases of neurodegeneration occurring in amyloid-based neurodegenerative diseases (prion, Alzheimer's, Parkinson's diseases, Amyotrophic Lateral Sclerosis). Even if these diseases have distinct etiologies and display specific clinical manifestations, they may share common neurodegenerative pathways. Based on in vitro and in vivo approaches, we aim to characterize those pathways. We evidenced common signaling cascades deregulated in prion and Alzheimer's diseases that contribute to synapse failure and axon retraction, the accumulation of the neurotoxic amyloids (pathogenic prions and Abeta), their brain deposition and the formation of amyloid plaques, and that render diseased neurons highly vulnerable to inflammation (Nature Medicine, 2013, Plos Pathogens, 2015, Scientific Reports, 2017, Nature Communications, 2019). Two kinases PDK1 et ROCK are critically involved in these deleterious events and emerge as therapeutic targets with a broad application spectrum to combat amyloid-based neurodegenerative diseases.