Heat shock protein defenses in the neocortex and allocortex of the telencephalon

NEUROBIOLOGY OF AGING

卷:36

Article

Posimo, Jessica M.¹  Weilnau, Justin N.¹  Gleixner, Amanda M.¹  Broeren, Matthew T.¹  Weiland, Nicole L.¹  Brodsky, Jeffrey L.²  Wipf, Peter^3,4  Leak, Rehana K.¹ 

[1] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA

[2] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

[4] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA

关键词: Alzheimer's disease;    Parkinson's disease;    Archicortex;    Paleocortex;    Heme oxygenase-1;    Hsp70;    Braak;    Entorhinal cortex;    Piriform cortex;    Hippocampus;   

DOI  :  10.1016/j.neurobiolaging.2015.02.011

来源: Elsevier

【 摘 要 】

The telencephalic allocortex develops protein inclusions before the neocortex in many age-related proteinopathies. One major defense mechanism against proteinopathic stress is the heat shock protein (Hsp) network. We therefore contrasted Hsp defenses in stressed primary neocortical and allocortical cells. Neocortical neurons were more resistant to the proteasome inhibitor MG132 than neurons from 3 allocortical subregions: entorhinal cortex, piriform cortex, and hippocampus. However, allocortical neurons exhibited higher MG132-induced increases in Hsp70 and heat shock cognate 70 (Hsc70). MG132-treated allocortical neurons also exhibited greater levels of protein ubiquitination. Inhibition of Hsp70/Hsc70 activity synergistically exacerbated MG132 toxicity in allocortical neurons more than neocortical neurons, suggesting that the allocortex is more reliant on these Hsp defenses. In contrast, astrocytes harvested from the neocortex or allocortex did not differ in their response to Hsp70/ Hsc70 inhibition. Consistent with the idea that chaperones are maximally engaged in allocortical neurons, an increase in Hsp70/Hsc70 activity was protective only in neocortical neurons. Finally, the levels of select Hsps were altered in the neocortex and allocortex in vivo with aging. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

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