Premium
P4–281: Targeting cyclooxygenase–derived levuglandins as potentially novel therapeutic approaches to Alzheimer's disease
Author(s) -
Boutaud Olivier,
Zagol-Ikapitte IrÃn̈e,
Amarnath Venkataraman,
Yermalitsky Valery,
Andreasson Katrin I.,
Montine Thomas J.,
Oates John A.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2020
Subject(s) - cyclooxygenase , lysine , chemistry , adduct , hippocampus , alzheimer's disease , gene isoform , prostaglandin e2 , cysteine , enzyme , genetically modified mouse , prostaglandin , senile plaques , biochemistry , pharmacology , transgene , medicine , disease , amino acid , gene , organic chemistry
ELISA-type assays, allowed the isolation of a panel of Nanobodies with different binding-capacity and specificity. Selected Nanobodies were characterized for their biochemical and immuno-histochemical specificity, respectively by Western blotting and on brain sections of APP[V717I] transgenic mice, our validated model for amyloid pathology in AD. The combination of classical and urea/SDS-PAGE with immunoblotting and histo-amyloid-reactivity resulted in the selection of several Nanobodies differing in specificity, i.e. reacting with all A , with A 42, and/or with amyloid plaques. The latter was confirmed in vivo by intra-cerebral injection. Conclusions: Based on the selected Nanobodies, we derived bivalent and bispecific Nanobodies that are directed to different molecular targets, as well as others that can actively pass the blood-brain barrier, aiming at therapeutic and diagnostic purposes.