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My current work is focused on the mechanisms underlying the toxicity of the amyloid proteins in neurodegenerative diseases (Alzheimer/Parkinson). With Pr Jacques Fantini, we have elucidated the molecular mechanisms that control the assembly of amyloid pores in the plasma membrane of brain cells. We designed a short (12 aa) chimeric peptide that combines the ganglioside-binding properties of Abeta and alpha-synuclein. This therapeutic peptide, now named AmyP53, acts at the earliest step of the amyloid oligomer-calcium cascade and protects the brain tissue against the neurotoxicity of amyloid oligomers. This drug candidate is the first representative of a new therapeutic class that inhibits a fundamental mechanism causing Alzheimer’s and Parkinson’s diseases. The AmyPore company (https://www.amypore.com) is now in charge of the development of AmyP53 as anti-Alzheimer/Parkinson medicine.
Overall, I have accumulated 33 years of research and teaching experience in virology and molecular biology. During the 1988-2002 period, I was interested in deciphering the molecular and cellular mechanisms underlying the pathogenicity of HIV viruses. With Professor J. Fantini, we have discovered the universal Sphingolipid-Binding Domain (SBD) in proteins with no sequence homology but sharing common structural features mediating membrane sphingolipid recognition. The SBD is evolutionary conserved and is present in a broad range of infectious and amyloid proteins, revealing common mechanisms of pathogenesis in both infectious and neurodegenerative diseases. During the last 20 years my idea was to find out how distinct pathologies are caused by common molecular mechanisms involving lipid-protein interactions within the plasma membrane. Our discovery of the SBD and, later, of the cholesterol-binding domain (CBD) in amyloid proteins has given a solid biochemical background to understand most proteinopathies and develop innovative strategies to treat these diseases. More recently, my experience in molecular virology has been applied to decipher the molecular mechanisms of SARS-CoV-2 infection, whith special emphasis to lipid raft and virus-gangliosides interactions.
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International Journal of Molecular Sciencesno. 2 (2023): 1760-1760
VIRUSES-BASELno. 9 (2023): 1854-1854
International Journal of Molecular Sciencesno. 2 (2023): 1760
Philippe Colson, Christian Lavagna,Jérémy Delerce, Guillaume Groshenry,Nouara Yahi,Jacques Fantini,Bernard La Scola,Thomas Althaus
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