GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

TableEdit

Jump to: navigation, search

PMID:16116427

You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor

Citation

Zhao, L, Longo-Guess, C, Harris, BS, Lee, JW and Ackerman, SL (2005) Protein accumulation and neurodegeneration in the woozy mutant mouse is caused by disruption of SIL1, a cochaperone of BiP. Nat. Genet. 37:974-9

Abstract

Endoplasmic reticulum (ER) chaperones and ER stress have been implicated in the pathogenesis of neurodegenerative disorders, such as Alzheimer and Parkinson diseases, but their contribution to neuron death remains uncertain. In this study, we establish a direct in vivo link between ER dysfunction and neurodegeneration. Mice homozygous with respect to the woozy (wz) mutation develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations reminiscent of protein inclusions in both the ER and the nucleus. In addition, upregulation of the unfolded protein response, suggestive of ER stress, occurs in mutant Purkinje cells. We report that the wz mutation disrupts the gene Sil1 that encodes an adenine nucleotide exchange factor of BiP, a crucial ER chaperone. These findings provide evidence that perturbation of ER chaperone function in terminally differentiated neurons leads to protein accumulation, ER stress and subsequent neurodegeneration.

Links

PubMed Online version:10.1038/ng1620

Keywords

Animals; Ataxia/etiology; Autoantigens/metabolism; Cell Nucleus/metabolism; Cerebellum/pathology; Endoplasmic Reticulum; Female; Guanine Nucleotide Exchange Factors/physiology; Heat-Shock Proteins/genetics; Heat-Shock Proteins/physiology; Homozygote; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Chaperones/genetics; Molecular Chaperones/physiology; Molecular Sequence Data; Mutation; Nerve Degeneration; Purkinje Cells/metabolism; Purkinje Cells/pathology

public



Cancel