Link between endoplasmic reticulum stress and autophagy in neurodegenerative diseases

Hosoi, Toru; Nomura, Jun; Tanaka, Keigo; Ozawa, Koichiro; Nishi, Akinori; Nomura, Yasuyuki

doi:10.1515/ersc-2017-0004

Cited by 6 publications

(5 citation statements)

References 75 publications

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“…IRE1/XBP1 pathway may influence the pathogenesis of neurodegenerative diseases. XBP1s acts as a transcription factor activating Beclin-1, the mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) [ 47 ]. In addition, XBP1-FoxO1 (Forkhead box protein O1) interaction regulates ER stress-induced autophagy [ 48 ].…”

Section: Er Stress and The Unfolded Protein Response (Upr)mentioning

confidence: 99%

Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases

Ghemrawi

Khair

2020

IJMS

188

130

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The endoplasmic reticulum (ER) is an important organelle involved in protein quality control and cellular homeostasis. The accumulation of unfolded proteins leads to an ER stress, followed by an adaptive response via the activation of the unfolded protein response (UPR), PKR-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) and activating transcription factor 6 (ATF6) pathways. However, prolonged cell stress activates apoptosis signaling leading to cell death. Neuronal cells are particularly sensitive to protein misfolding, consequently ER and UPR dysfunctions were found to be involved in many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and prions diseases, among others characterized by the accumulation and aggregation of misfolded proteins. Pharmacological UPR modulation in affected tissues may contribute to the treatment and prevention of neurodegeneration. The association between ER stress, UPR and neuropathology is well established. In this review, we provide up-to-date evidence of UPR activation in neurodegenerative disorders followed by therapeutic strategies targeting the UPR and ameliorating the toxic effects of protein unfolding and aggregation.

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Section: Er Stress and The Unfolded Protein Response (Upr)mentioning

confidence: 99%

Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases

Ghemrawi

Khair

2020

IJMS

188

130

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“…In hypoxic tumor xenografts, expression of autophagic factor LC3 has been reported to enhance autophagy survival mechanism (89). During hypoxia-induced ER stress, PERK, promotes autophagosome formation by transcriptional upregulation of microtubule associated protein 1 light chain 3 beta (MAP1LC3) and autophagy regulated (ATG) 5 through ATF4 and CHOP respectively (89,96,97). Moreover, eIF2α/ATF4/CHOP axis regulates the transcriptional levels of p62 and promotes autophagy induction through binding with the amino acid response element (AARE) sequence of p62 promoter (59).…”

Section: The Upr Controls Apoptosis and Autophagy In Response To Cell Stress In Cancermentioning

confidence: 99%

Regulation of autophagy by canonical and non-canonical ER stress responses

Bhardwaj

Leli

Koumenis

et al. 2020

Seminars in Cancer Biology

136

116

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“…The data obtained so far suggest the need to investigate the involvement of URG7 in autophagy, one of the mechanisms that allows neuronal cells to eliminate the excess of proteins under proteotoxic stress [ 36 , 37 , 38 , 39 ]. As can be seen in Figure 5 E,F, under ER stress conditions, the up-regulation of both LC3-II and Beclin-1 proteins, both involved in the formation process of the autophagosome, was found in cells overexpressing URG7.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y

Nigro,

Miglionico,

Carmosino

et al. 2023

IJMS

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Up-regulated Gene clone 7 (URG7) is a protein localized in the endoplasmic reticulum (ER) and overexpressed in liver cells upon hepatitis B virus (HBV) infection. Its activity has been related to the attenuation of ER stress resulting from HBV infection, promoting protein folding and ubiquitination and reducing cell apoptosis overall. While the antiapoptotic activity of URG7 in HBV-infected cells may have negative implications, this effect could be exploited positively in the field of proteinopathies, such as neurodegenerative diseases. In this work, we aimed to verify the possible contribution of URG7 as a reliever of cellular proteostasis alterations in a neuronal in vitro system. Following tunicamycin-induced ER stress, URG7 was shown to modulate different markers of the unfolded protein response (UPR) in favor of cell survival, mitigating ER stress and activating autophagy. Furthermore, URG7 promoted ubiquitination, and determined a reduction in protein aggregation, calcium release from the ER and intracellular ROS content, confirming its pro-survival activity. Therefore, in light of the results reported in this work, we hypothesize that URG7 offers activity as an ER stress reliever in a neuronal in vitro model, and we paved the way for a new approach in the treatment of neurodegenerative diseases.

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Link between endoplasmic reticulum stress and autophagy in neurodegenerative diseases

Cited by 6 publications

References 75 publications

Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases

Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases

Regulation of autophagy by canonical and non-canonical ER stress responses

Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y

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