sodium-dodecyl-sulfate and Nerve-Degeneration

Metallothionein-III (MT-III) protects cerebral cortical neurons in established culture from the toxic effect of amyloid beta peptides (Abetas). Protection is concentration dependent and approaches 100% at 0.1 microM. The EC(50) value estimated at 5 microM Abeta(1-40) is 2 nM. At higher concentrations (>0.1 microM), MT-III also antagonizes the trophic effect of Abeta(1-40) on cerebral cortical neurons in early cultures. Because only the fibrillar, SDS-resistant form of Abeta aggregates are thought to be neurotoxic, we analyzed and compared Abeta(1-40) aggregates formed in the presence and absence of MT-III using SDS-PAGE. Results show that aggregates formed in the absence of MT-III are predominantly SDS-resistant whereas those formed in its presence are mostly SDS-soluble. Neither MT-I nor -II exhibits any of the effects of MT-III. On the basis of these results, we propose that MT-III alleviates Abetas' neurotoxic effect by abolishing the formation of toxic aggregates of Abetas and that it may play a specific and important role in protecting the brain from the deleterious effects of Abetas.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cells, Cultured; Cerebral Cortex; Electrophoresis, Polyacrylamide Gel; Humans; Metallothionein 3; Nerve Degeneration; Nerve Growth Factors; Nerve Regeneration; Nerve Tissue Proteins; Neurons; Neurotoxins; Rats; Sodium Dodecyl Sulfate

Topics: Animals; Electrophoresis; Isoniazid; Male; Microscopy, Electron; Myelin Sheath; Nerve Degeneration; Nerve Tissue Proteins; Rats; Schwann Cells; Sciatic Nerve; Sodium Dodecyl Sulfate

Topics: Animals; Centrifugation, Density Gradient; Chromatography, Thin Layer; Densitometry; Electrophoresis, Polyacrylamide Gel; Lipids; Microscopy, Electron; Myelin Sheath; Nerve Degeneration; Optic Nerve; Proteins; Rats; Sodium Dodecyl Sulfate; Sucrose; Time Factors