The environmental ncurotoxin aluminum exerts several distinct biochemical effects on neurofilament proteins, including subunit agg~gation, disruption of the normal segregation of phospho~lated subunits within axons leading to abnormal perikaryal accumulation, and inhibition of in vitro degradation by the calcium-dependent neutral protease0 ealpain. In the present study, we demonstrate that exposure of mouse CNS cytosk~letal preparations to aluminum chloride inhibits the degradation of neurofilament proteins by both calcium-del~ndcnt and -independent prot~scs that co-purify with eytoskeletons. Aluminum inhibited both clacium-dependent and calcium.independent proteolysls of the high and middle mol~ular weight neurofilament subunits, but inhibited only calcium-dependent, and not calcium-independent proteolysls of the low mol~alar w¢iBht neurofilament subunit. These findings demonstrate that aluminum interferes with multiple aspects of neurofilament protein metabolism.
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