Aluminum induces neurofilament aggregation by stabilizing cross-bridging of phosphorylated c-terminal sidearms

  title={Aluminum induces neurofilament aggregation by stabilizing cross-bridging of phosphorylated c-terminal sidearms},
  author={Jacob Kushkuley and Shailesh R Metkar and Walter K-H Chan and Sangmook Lee and Thomas B. Shea},
  journal={Brain Research},

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It is observed that perikarya of cells exposed to both aluminum and the protease inhibitor C1 were more intensely labeled by monoclonal antibodies directed against both nonphosphorylated and phosphorylated epitopes than were cells treated with either aluminum or protease inhibitors alone.

Calcium modulates aluminum neurotoxicity and interaction with neurofilaments.

  • T. Shea
  • Biology
    Molecular and chemical neuropathology
  • 1995
AlCl3 (1 mM) retards the electrophoretic migration of NF subunits on SDS-gels, and the presence of CaCl2 alone did not alter NF migration, underscore the possibility that multiple factors, including those that compromise general neuronal homeostasis, may contribute to neurofibrillary pathology.

Aluminum Inhibits Calpain‐Mediated Proteolysis and Induces Human Neurofilament Proteins to Form ProteaseResistant High Molecular Weight Complexes

Interactions of aluminum with neurofilament proteins and the effects on proteolysis suggest possible mechanisms for the impaired axoplasmic transport of neurofilaments and their accumulation in neuronal perikarya after aluminum administration in vivo.

A Molecular Mechanism for the Induction of Neurofilament Bundling by Aluminum Ions

Immunoblotting analysis of neurofilaments in cultivated neurons intoxicated with Al compounds revealed a similar Al‐dependent alteration of the neurofilament subunit conformation, suggesting that the mechanism of Al‐induced bundling of neuro filaments derived from in vitro studies might be involved in the formation of tangles in situ.

Aluminum inhibits neurofilament assembly, cytoskeletal incorporation, and axonal transport. Dynamic nature of aluminum-induced perikaryal neurofilament accumulations as revealed by subunit turnover.

It is demonstrated that aluminum interferes with multiple aspects of neurofilament dynamics and furthermore leaves open the possibility that aluminum-induced perikaryal NF whorls may not represent permanent structures, but rather may require continued recruitment of cytoskeletal constituents.

Aluminum Alters the Electrophoretic Properties of Neurofilament Proteins: Role of Phosphorylation State

A direct effect of aluminum on NFPs is demonstrated and a possible mechanism for neurofilament accumulation in perikarya during aluminum intoxication is provided, resulting in intermolecular cross‐linking.

Relative susceptibility of cytoskeleton-associated and soluble neurofilament subunits to aluminum exposure in intact cells. A possible mechanism for reduction of neurofilament axonal transport during aluminum neurotoxicity.

Aluminum may exert a relatively greater effect on NF subunits that have not yet undergone axonal transport and/or incorporation into Triton-insoluble structures vs those that have already deposited into axons, as suggested by the observation that a higher concentration of aluminum was required to alter the electrophoretic migration of in vitro reassembled neurofilaments vs that required for unassembled NF subunit.

Aluminum treatment of intact neuroblastoma cells alters neurofilament subunit phosphorylation, solubility, and proteolysis.

Direct effects of aluminum on neurofilament subunits within intact neuronal cells similar to those previously demonstrated following in vitro exposure of isolated neurofilaments to aluminum are demonstrated.