Aluminum induces the in vitro aggregation of bovine brain cytoskeletal proteins.

The addition of aluminum to purified cytoskeletal proteins in vitro selectively induces the aggregation of highly phosphorylated proteins, such as the two larger neurofilament subunits (200 and 160 kDa) and the microtubule-associated proteins of the MAP-1 group (MAP-1A and MAP-1B). Other cytoskeletal proteins with a substantially lower phosphate content, such as the smaller neurofilament subunit (68 kDa) and tubulin, remain soluble, even in the presence of high aluminum concentrations. This suggests that aluminum interacts with phosphate groups in cytoskeletal proteins, causing their precipitation. The protein aggregates formed in the presence of aluminum are resistant to reagents such as urea and sodium dodecyl sulphate (SDS) which dissolve normal cytoskeletal polymers (neurofilaments and microtubules). These results favor the view that the neurotoxic effect of aluminum may be due primarily to the disorganization of the neuronal cytoskeleton which may occur subsequent to the precipitation of certain highly phosphorylated cytoskeletal proteins.