ALUMINUM INHIBITS NEUROFILAMENT PROTEIN-DEGRADATION BY MULTIPLE CYTOSKELETON-ASSOCIATED PROTEASES

The environmental neurotoxin aluminum exerts several distinct biochemical effects on neurofilament proteins, including subunit aggregation, disruption of the normal segregation of phosphorylated subunits within axons leading to abnormal perikaryal accumulation, and inhibition of in vitro degradation by the calcium-dependent neutral protease, calpain. In the present study, we demonstrate that exposure of mouse CNS cytoskeletal preparations to aluminum chloride inhibits the degradation of neurofilament proteins by both calcium-dependent and -independent proteases that co-purify with cytoskeletons. Aluminum inhibited both calcium-dependent and calcium-independent proteolysis of the high and middle molecular weight neurofilament subunits, but inhibited only calcium-dependent, and not calcium-independent proteolysis of the low molecular weight neurofilament subunit. These findings demonstrate that aluminum interferes with multiple aspects of neurofilament protein metabolism.