The solubilization of model Alzheimer tangles: reversing the beta-sheet conformation induced by aluminum with silicates.

Abstract

Neurofibrilary tangles are one of two lesions found In the brain ofAl disease victims. With synthetic peptide ents of human neuroflament NF-M17 (Glu-GluLys-Gly-Lys-Ser-Pro-Val-Pro-Lys-Ser-Pro-Val-Glu-Glu-LysGly, pbosphorylated and unphophorlated), CD studies were done to examine the e fect o sodium orthosilicate on the conformatfional state produced by Al+ on faments of neuronal proteins. Previous studies had shown a conformational transiion from a-helix and random to «-pleated sheet upon additionof AP+ to both phosphorylated and unphos lated peptides. If sufcent qmtities of AP+ are added, the peptide precipitates from solution. The abity to reverse or 1ow the of aggregaion was exmned. A13+ binding was reversed with 1-2 molar equivalents of sodium orthosilicate (with respect to A3+), altering the conformation from -sheet to random coil and r ig in a CD spectrum ilar to that of the initial peptide. The tight binding of the SlO4 with the AI3+ apds the mechn for this tantn. These results provide a i inormation toward understanding the role of aium in the Mhlmer did brain and suggest the investigation of the possible use of sites as a therapeutic agent.

Aluminium in Alzheimer?s disease: are we still at a crossroad?

“…The toxic effect of Al has been shown to be reduced in the presence of silicic acid due the formation of hydroxyaluminosilicates. It has been also found that sodiumorthosilicates could reverse Al +3 -induced b-sheet conformation in neurofilament protein (NF-M17) [108]. This has been attributed to the high binding constant of SiO 4 -4 with Al +3 .…”

“…This has been attributed to the high binding constant of SiO 4 -4 with Al +3 . Based on the contributions, it has been hypothesized that silicates may serve as a possible preventive treatment for individuals showing early symptoms of AD or as a method of retarding the advance of the disease [108]. Thus it seems that metal-metal interrelations play a significant role, but further peer-reviewed data are needed in this area.…”

Acrylamide-Induced Changes in the Neurofilament Protein of Rat Cerebrum Fractions

“…Over expression of a single NF subunit in transgenic mice has resulted in abnormal accumulation of NF proteins followed by axonal degeneration and hindlimb paralysis of the animals (13). Accumulation of NFs has also been observed in animals exposed to 2,5-hexanedione (14), aluminum (15), IDPN (16), and organophosphate-induced delayed neurotoxicity (OPIDN) (17,18).…”

Nanoparticles for the Treatment ofAlzheimer's Disease: Theoretical Rationale, Present Status and Future Perspectives

“…The functional groups of the prochelator are then activated by enzymatic or nonenzymatic reactions after they have entered the target organ [121]. Another example is to use simple inorganic silicate that can form very stable complexes with many metals and probably has the ability to enter the BBB [348]. A newly developed copper chelator (tetrathiomolybdate) for Wilson's disease is also suggested as a potential treatment for AD [85,349].…”