Amelioration of neuronal cell death in a spontaneous obese rat model by dietary restriction through modulation of ubiquitin proteasome system

2016 ◽  
Vol 33 ◽  
pp. 73-81 ◽  
Author(s):  
Karnam Shruthi ◽  
S. Sreenivasa Reddy ◽  
P. Yadagiri Reddy ◽  
Potula Shivalingam ◽  
Nemani Harishankar ◽  
...  
Keyword(s):  
Cell Death ◽  
Dietary Restriction ◽  
Rat Model ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome

Altered ubiquitin-proteasome system leads to neuronal cell death in a spontaneous obese rat model

2014 ◽  
Vol 1840 (9) ◽  
pp. 2924-2934 ◽  
Author(s):  
S. Sreenivasa Reddy ◽  
Karnam Shruthi ◽  
V. Sudhakar Reddy ◽  
G. Raghu ◽  
P. Suryanarayana ◽  
...  
Keyword(s):  
Cell Death ◽  
Rat Model ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome

Degradation of mutant huntingtin via the ubiquitin/proteasome system is modulated by FE65

2012 ◽  
Vol 443 (3) ◽  
pp. 681-689 ◽  
Author(s):  
Wan Ning Vanessa Chow ◽  
Hon Wing Luk ◽  
Ho Yin Edwin Chan ◽  
Kwok-Fai Lau
Keyword(s):  
Cell Death ◽  
Degradation Mechanism ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Adaptor Protein ◽  
Ubiquitin Proteasome System ◽  
Exon 1 ◽  
Ubiquitin Proteasome

An unstable expansion of the polyglutamine repeat within exon 1 of the protein Htt (huntingtin) causes HD (Huntington's disease). Mounting evidence shows that accumulation of N-terminal mutant Htt fragments is the source of disruption of normal cellular processes which ultimately leads to neuronal cell death. Understanding the degradation mechanism of mutant Htt and improving its clearance has emerged as a new direction in developing therapeutic approaches to treat HD. In the present study we show that the brain-enriched adaptor protein FE65 is a novel interacting partner of Htt. The binding is mediated through WW–polyproline interaction and is dependent on the length of the polyglutamine tract. Interestingly, a reduction in mutant Htt protein level was observed in FE65-knockdown cells, and the process requires the UPS (ubiquitin/proteasome system). Moreover, the ubiquitination level of mutant Htt was found to be enhanced when FE65 is knocked down. Immunofluroescence staining revealed that FE65 associates with mutant Htt aggregates. Additionally, we demonstrated that overexpression of FE65 increases mutant Htt-induced cell death both in vitro and in vivo. These results suggest that FE65 facilitates the accumulation of mutant Htt in cells by preventing its degradation via the UPS, and thereby enhances the toxicity of mutant Htt.

scholarly journals E2-25K/Hip-2 regulates caspase-12 in ER stress–mediated Aβ neurotoxicity

2008 ◽  
Vol 182 (4) ◽  
pp. 675-684 ◽  
Author(s):  
Sungmin Song ◽  
Huikyong Lee ◽  
Tae-In Kam ◽  
Mei Ling Tai ◽  
Joo-Yong Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Cortical Neurons ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Ubiquitin Proteasome System ◽  
Proteolytic Activation ◽  
Upstream Regulator ◽  
Caspase 12

Amyloid-β (Aβ) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Aβ neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)–resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. Aβ increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2–mediated cell death. Finally, we find that E2-25K/Hip-2–deficient cortical neurons are resistant to Aβ toxicity and to the induction of ER stress and caspase-12 expression by Aβ. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress–mediated Aβ neurotoxicity.

Treatment with atacicept enhances neuronal cell death in a rat model of optic neuritis

2014 ◽  
Vol 268 (1-2) ◽  
pp. 58-63 ◽  
Author(s):  
Benedikt Kretzschmar ◽  
Katharina Hein ◽  
Zahra Moinfar ◽  
Birte Könnecke ◽  
Muriel B. Sättler ◽  
...  
Keyword(s):  
Cell Death ◽  
Optic Neuritis ◽  
Rat Model ◽  
Neuronal Cell Death ◽  
Neuronal Cell
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