Apoptotic death of neurons exhibiting peripherin aggregates is mediated bythe proinflammatory cytokine tumor necrosis factor-alpha

Citation
J. Robertson et al., Apoptotic death of neurons exhibiting peripherin aggregates is mediated bythe proinflammatory cytokine tumor necrosis factor-alpha, J CELL BIOL, 155(2), 2001, pp. 217-226
Citations number
74
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
155
Issue
2
Year of publication
2001
Pages
217 - 226
Database
ISI
SICI code
0021-9525(20011015)155:2<217:ADONEP>2.0.ZU;2-V
Abstract
Peripherin, a neuronal intermediate filament protein associated with axonal spheroids in amyotrophic lateral sclerosis (ALS), induces the selective de generation of motor neurons when overexpressed in transgenic mice. To furth er clarify the selectivity and mechanism of peripherin-induced neuronal dea th, we analyzed the effects of peripherin overexpression in primary neurona l cultures. Peripherin overexpression led to the formation of cytoplasmic p rotein aggregates and caused the death not only of motor neurons, but also of dorsal root ganglion (DRG) neurons that were cultured from dissociated s pinal cords of peripherin transgenic embryos. Apoptosis of DRG neurons cont aining peripherin aggregates was dependent on the proinflammatory central n ervous system environment of spinal cultures, rich in activated microglia, and required TNF-alpha. This synergistic proapoptotic effect may contribute to neuronal selectivity in ALS.