Replies to post #23349 on Rock Creek Pharmaceuticals Inc. (fka RCPIQ)

[Buddhahead]

And don't forget: Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice in 'Brain Disorders & Therapy', Daniel Paris1*, David Beaulieu-Abdelahad1, Ghania Ait-Ghezala1, Venkat Mathura1, Megha Verma1, Alex E Roher3, Jon Reed1,Fiona Crawford1 and Michael Mullan1,2
1Roskamp Institute, Sarasota, Florida, USA
2Rock Creek Pharmaceuticals

Abstract:

We have previously shown that the natural alkaloid anatabine displays some anti-inflammatory and Alzheimer amyloid (Aß) lowering properties in the central nervous system associated with reduced STAT3 and NFkB activation. We investigated here the impact of a chronic oral treatment with anatabine in a model of tauopathy. We found that anatabine reduces the incidence of paralysis and abnormal hind limb extension reflex while improving rotarod performances in P301S mutant human Tau transgenic mice (Tg Tau P301S) suggesting that anatabine delays the disease progression in this model of tauopathy. Analyzes of brain and spinal cord homogenates reveal that anatabine reduces tau phosphorylation at multiple pertinent Alzheimer’s disease (AD) epitopes and decreases the levels of pathological tau conformers/oligomers in both detergent soluble and insoluble fractions. Pathological tau species reduction induced by anatabine was accompanied by decreased Iba1 expression suggesting a diminution of microgliosis in the brain and spinal cord of Tg Tau P301S mice. In addition, we found that anatabine administration increases phosphorylation of the inhibitory residue (Ser9) of glycogen synthase kinase-3ß, a primary tau kinase, associated with AD pathology, providing a possible mechanism for the observed reduction of tau phosphorylation. These data support further exploration of anatabine as a possible disease modifying agent for neurodegenerative tauopathies and, in particular AD, since anatabine also displays Aß lowering properties.