Ubiquitin pathways in neurodegenerative disease

Atkin, Graham; Paulson, Henry L.

doi:10.3389/fnmol.2014.00063

Cited by 124 publications

(109 citation statements)

References 217 publications

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“…This comes as no surprise, as glutamate can induce an endoplasmic reticulum stress-associated death signalling cascade in neuronal cells [28] resembling the unfolded protein response known to promote a global transcriptional reprogramming [29]. The particular finding also supports the speculation that the observed up-regulation in protein levels of these chaperones is caused probably by post-translational modifications known to block protein turnover and promote protein stability, such as ubiquitination [30], which needs further investigation.…”

Section: Discussionsupporting

confidence: 54%

Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

Stamoula

Vavilis

Aggelidou

et al. 2015

Cell Physiol Biochem

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Background/Aims: Increasing amounts of the neurotransmitter glutamate are associated with excitotoxicity, a phenomenon related both to homeostatic processes and neurodegenerative diseases such as multiple sclerosis. Methods: PC12 cells (rat pheochromocytoma) were treated with various concentrations of the non-essential amino acid glutamate for 0.5-24 hours. The effect of glutamate on cell morphology was monitored with electron microscopy and haematoxylin-eosin staining. Cell survival was calculated with the MTT assay. Expression analysis of chaperones associated with the observed phenotype was performed using either Western Blotting at the protein level or qRT-PCR at the mRNA level. Results: Administration of glutamate in PC12 cells in doses as low as 10 μM causes an up-regulation of GRP78, GRP94 and HSC70 protein levels, while their mRNA levels show the opposite kinetics. At the same time, GAPDH and GRP75 show reduced protein levels, irrespective of their transcriptional rate. On a cellular level, low concentrations of glutamate induce an autophagy-mediated pro-survival phenotype, which is further supported by induction of the autophagic marker LC3. Conclusion: The findings in the present study underline a discrete effect of glutamate on neuronal cell fate depending on its concentration. It was also shown that a low dose of glutamate orchestrates a unique expression signature of various chaperones and induces cell autophagy, which acts in a neuroprotective fashion.

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Section: Discussionsupporting

confidence: 54%

Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

Stamoula

Vavilis

Aggelidou

et al. 2015

Cell Physiol Biochem

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“…It is an E3 ubiquitin ligase protein, which interacts with HSC70-HSP70 and HSP90 and helps substrate ubiquitination and degradation of misfolded protein by the proteasome system [73]. CHIP serves as a link between the folding-refolding machinery in proteasome degradation pathways and has a direct role in a particular protein quality control pathway [74].…”

Section: Although the Mechanistic Details Of Neuroprotection By Cur Imentioning

confidence: 99%

Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

Maiti¹,

Rossignol²,

Dunbar³

2017

J Alzheimers Dis Parkinsonism

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“…Several studies on AD have shown that various proteins are subjected to modifications such as phosphorylation, ubiquitination, and more recently, SUMOylation [24][25][26][27][28].…”

Section: Sumoylation In Admentioning

confidence: 99%

Battling Alzheimer’s Disease: Targeting SUMOylation-Mediated Pathways

2015

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SUMO (small ubiquitin-like modifier) conjugation is a critically important control process in all eukaryotic cells, because it acts as a biochemical switch and regulates the function of hundreds of proteins in many different pathways. Although the diverse functional consequences and molecular targets of SUMOylation remain largely unknown, SUMOylation is becoming increasingly implicated in the pathophysiology of Alzheimer's disease (AD). Apart from the central SUMO-modified disease-associated proteins, such as amyloid precursor protein, amyloid β, and tau, SUMOylation also regulates several other processes underlying AD. These are involved in inflammation, mitochondrial dynamics, synaptic transmission and plasticity, as well as in protective responses to cell stress. Herein, we review current reports on the involvement of SUMOylation in AD, and present an overview of potential SUMO targets and pathways underlying AD pathogenesis.

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Ubiquitin pathways in neurodegenerative disease

Cited by 124 publications

References 217 publications

Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

Low Dose Administration of Glutamate Triggers a Non-Apoptotic, Autophagic Response in PC12 Cells

Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

Battling Alzheimer’s Disease: Targeting SUMOylation-Mediated Pathways

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