Dr. Somdatta Ghosh Dey ,
Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata, India
Titre : Alzheimer’s Disease : A Heme Perspective.
Date : Jeudi 1er juin 2017 à 12h00.
Lieu : Salle des séminaires de l’Institut Jacques Monod, Bâtiment Buffon, 15 rue Hélène Brion, pièce RdC Bas 18B, Université Paris Diderot, campus PRG
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that has generally been associated with the accumulation of amyloid beta (Aβ) peptides and formation of partially reduced oxygen species (PROS) catalyzed by Cu bound Aβ active sites in the brain. Heme binding to Aβ peptides has opened up a new direction in this field. The presentation will summarize our take on the potential role of heme bound Aβ peptides (heme-Aβ) in AD and the related biophysics of these entities. We define the active site of heme-Aβ using several spectroscopic techniques and site directed mutagenesis. The heme-Aβ peptides can act as peroxidases and degrade neurotransmitters like serotonin. These entities can interact with physiologically available redox active metals like Cu and signaling molecules like NO and CO. They can use cytochrome c as redox partners and donate the heme to proteins like myoglobin and neuroglobin. These interactions and their mechanism of action will be detailed and the role of 2nd sphere residues like Tyr10 and Arg5, which are absent in species which do not develop AD, will be illustrated. The talk will end with a parting thought : is AD type 3 diabetes or is diabetes AD of the pancreas ?
