Role of CD36 in cerebrovascular dysfunction in a mouse model of Alzheimer´s disease
Final Report Abstract
In a first step we were able to identify CD36 as an important mediator of Aß induced cerebrovascular dysfunction through NADPH oxidase activation and the production of reactive oxygen species (superoxide). In further steps, we investigated the relevant players involved in this process of disruption of cerebrovascular blood flow. We found that peroxynitrite, which is formed by NADPH oxidase derived superoxide and nitric oxide synthase derived nitric oxide, activated poly (ADP-ribose) polymerase (PARP)-1. PARP-1, in turn, mediated the deleterious cerebrovascular effects of Aß. Thus, inhibition of peroxynitrite formation and/or PARP-1 activation might be promising targets to prevent Aß induced cerebrovascular dysfunction in amyloid associated diseases.
Publications
- Neurovascular protection by Ischemic-tolerance: role of NO. J Physiol 2011
Costantino ladecola, Timo Kahles, Eduardo Gallo, Josef Anrather
(See online at https://doi.org/10.1113/jphysiol.2011.210831) - NADPH oxidases as therapeutic targets in ischemic stroke. Cell Mol Life Sci 2012
Timo Kahles, Ralf Brandes
(See online at https://doi.org/10.1007/s00018-012-1011-8) - Which NADPH oxidase isoform is relevant for stroke? The case for Nox 2. Antioxid Red Signal 2012
Timo Kahles, Ralf Brandes
(See online at https://doi.org/10.1089/ars.2012.4721)
