Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α

Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal dea...

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Veröffentlicht in:The Journal of cell biology 2001-10, Vol.155 (2), p.217-226
Hauptverfasser: Robertson, Janice, Beaulieu, Jean-Martin, Doroudchi, Mohammad M., Durham, Heather D., Julien, Jean-Pierre, Mushynski, Walter E.
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container_end_page 226
container_issue 2
container_start_page 217
container_title The Journal of cell biology
container_volume 155
creator Robertson, Janice
Beaulieu, Jean-Martin
Doroudchi, Mohammad M.
Durham, Heather D.
Julien, Jean-Pierre
Mushynski, Walter E.
description Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective degeneration of motor neurons when overexpressed in transgenic mice. To further clarify the selectivity and mechanism of peripherin-induced neuronal death, we analyzed the effects of peripherin overexpression in primary neuronal cultures. Peripherin overexpression led to the formation of cytoplasmic protein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated spinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons containing peripherin aggregates was dependent on the proinflammatory central nervous system environment of spinal cultures, rich in activated microglia, and required TNF-α. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS.
doi_str_mv 10.1083/jcb.200107058
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subjects Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - pathology
Animals
Antibodies
Antibodies - pharmacology
Apoptosis
Cell aggregates
Cells, Cultured
Cellular biology
Cultured cells
Cytokines
Ganglia, Spinal - ultrastructure
Intermediate Filament Proteins - genetics
Intermediate Filament Proteins - ultrastructure
Membrane Glycoproteins
Mice
Mice, Transgenic
Microglia
Microglia - metabolism
Microinjections
Motor neurons
Motor Neurons - ultrastructure
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - ultrastructure
Neurons
Peripherins
Proteins
Spinal cord
Spinal Cord - physiology
Transgenic animals
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - physiology
Tumors
title Apoptotic Death of Neurons Exhibiting Peripherin Aggregates Is Mediated by the Proinflammatory Cytokine Tumor Necrosis Factor-α
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