Cationic phosphorus dendrimers and therapy for Alzheimer's disease

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the aggregation of extracellular b-amyloid and the intracellular microtubule-associated protein Tau. Neurodegeneration is associated inter alia with the activation of microglial cells, neuroinflammation, oxidative stress, and diminished transduction of impulses in cholinergic neurons. Current pharmacotherapy for AD is based mainly on modulation of acetylcholine hydrolysis, administration of non-steroidal anti-inflammatory drugs and antioxidants. Novel drugs with antiamyloidic properties are currently being sought. Cationic phosphorus dendrimers have been proven to modulate amyloidogenesis and stop the aggregation of Tau protein. An ideal drug for AD should demonstrate anti-inflammatory properties, inhibit acetylcholine hydrolysis, and have antioxidant capacity. Cationic phosphorus dendrimers (generation 3 and generation 4) show the foregoing properties. They inhibit acetylcholinesterase activity, can decrease the secretion of TNF-a, and have weak antioxidant effects. The results presented suggest that phosphorus dendrimers may be considered in the future as agents in AD therapy.

Multi-Target Inhibition of Cancer Cell Growth by SiRNA Cocktails and 5-Fluorouracil Using Effective Piperidine-Terminated Phosphorus Dendrimers

“…CPD have been previously investigated in numerous biomedical applications [8][9][10][11][12]. With regard to transfection studies, most widely investigated group of CPD is diethylamine-terminated dendrimers with cyclotriphosphazene core.…”

Synthesis and characterization of bifunctional dendrimers: preliminary use for the coating of gold surfaces and the proliferation of human osteoblasts (HOB)

“…40 In the case of phosphorus dendrimers, positively charged dendrimers with the same ammonium terminal groups than 6-G 1 (but without the thioctic arm) have been used in many cases in contact with cells, as transfection agents, 29 as anti-HIV agents, 41 as in vivo anti-prion agents, 42 and as agents against the aggregation of Alzheimer's peptides. 43 No acute toxicity was observed, except in the case of human mononuclear blood cells, the polycationic dendrimers inducing changes in their morphology, and also the loss of cell attachment properties. 44 Negatively charged phosphorus dendrimers have many properties for modulating in vitro the response of the human immune system, 45 and have also anti-inflammatory properties in vivo.…”

Targeted Nanoparticles for the Treatment of Alzheimer's Disease

“…Due to their structure they can carry different drugs in the core [148]. Dendrimers behavior has been analyzed in mouse microglial cells and mouse neuroblastoma cells in sight of their more in-depth study for Alzheimer applications [149].…”