Anti-amyloidogenic amphipathic arginine-dehydrophenylalanine spheres capped selenium nanoparticles as potent therapeutic moieties for Alzheimer's disease

Aggregation of both amyloid beta (A & beta;) peptide and hyperphosphorylated tau proteins is the major pathological hallmark of Alzheimer's disease (AD). Moieties that carry anti-amyloidogenic potency against both of the aggregating entities are considered to be promising drug candidatures for the disease. In the current work, we have synthesized amphipathic dipeptide vesicle-templated selenium nanoparticles (R & UDelta;F-SeNPs) as potential entities to combat AD. We have investigated and established their anti-amyloidogenic activity against different peptide-based amyloid models, such as the reductionist model based on the dipeptide phenylalanine-phenylalanine (FF) derived from A & beta;; a model based on the hexapeptide Ac-PHF6 ((306)VQIVYK(311)) derived from tau protein; and the full-length A & beta;42 polypeptide-based model. We also evaluated the neuroprotective characteristics of R & UDelta;F-SeNPs against FF, Ac-PHF6, and A & beta;42 fibril-induced toxicity in neuroblastoma, SH-SY5Y cells. R & UDelta;F-SeNPs further exhibited neuroprotective effects in streptozotocin (STZ) treated neuronal (N2a) cells carrying AD-like features. In addition, studies conducted in an intra-cerebroventricular STZ-instigated rat model of dementia revealed that R & UDelta;F-SeNP-treated animals showed improved cognitive activity and reduced A & beta;42 aggregate burden in brain tissues as compared with the STZ-treated group. Moreover, in vivo brain distribution studies conducted in animal models additionally demonstrated the brain-homing ability of R & UDelta;F-SeNPs. All together, these studies supported the potency of R & UDelta;F-SeNPs as efficient and propitious disease-modifying therapeutic agents for combating AD.