The Endoplasmic Reticulum Stress/Unfolded Protein Response and Their Contributions to Parkinson’s Disease Physiopathology

Costa, Cristine Alves da; Manaa, Wejdane El; Duplan, Eric; Checler, Frédéric

doi:10.3390/cells9112495

Cited by 62 publications

(34 citation statements)

References 213 publications

(238 reference statements)

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“…Emerging evidence suggests that these disadvantages can perturb the balance of cellular homeostasis (proteostasis) in PD ( Lehtonen et al, 2019 ). Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways that respond to an imbalance in cellular homeostasis, play particularly important roles in the pathology of neurodegenerative diseases including PD ( Karabiyik et al, 2017 ; Costa et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Ren

Zhai

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, and it is characterized by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), as well as the presence of intracellular inclusions with α-synuclein as the main component in surviving DA neurons. Emerging evidence suggests that the imbalance of proteostasis is a key pathogenic factor for PD. Endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and autophagy, two major pathways for maintaining proteostasis, play important roles in PD pathology and are considered as attractive therapeutic targets for PD treatment. However, although ER stress/UPR and autophagy appear to be independent cellular processes, they are closely related to each other. In this review, we focused on the roles and molecular cross-links between ER stress/UPR and autophagy in PD pathology. We systematically reviewed and summarized the most recent advances in regulation of ER stress/UPR and autophagy, and their cross-linking mechanisms. We also reviewed and discussed the mechanisms of the coexisting ER stress/UPR activation and dysregulated autophagy in the lesion regions of PD patients, and the underlying roles and molecular crosslinks between ER stress/UPR activation and the dysregulated autophagy in DA neurodegeneration induced by PD-associated genetic factors and PD-related neurotoxins. Finally, we indicate that the combined regulation of ER stress/UPR and autophagy would be a more effective treatment for PD rather than regulating one of these conditions alone.

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Section: Introductionmentioning

confidence: 99%

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Ren

Zhai

et al. 2021

Front. Aging Neurosci.

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“…ER stress is a state in which an external stimulus disrupts ER homeostasis and triggers the accumulation of unfolded or misfolded proteins within the ER lumen [72]. Calcium overload and abnormal lipid metabolism, due to ER dysregulation, will further promote ER stress [73]. The stimuli thought to cause ER stress include nutritional deficiency, hypoxia, ischemia, oxidative stress, and DNA damage [74][75][76].…”

Section: Molecular Basis Of Er Stressmentioning

confidence: 99%

Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia‐Reperfusion Injury

Zhu

Zhou

2021

Oxidative Medicine and Cellular Longevity

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Impaired function of the endoplasmic reticulum (ER) is followed by evolutionarily conserved cell stress responses, which are employed by cells, including cardiomyocytes, to maintain and/or restore ER homeostasis. ER stress activates the unfolded protein response (UPR) to degrade and remove abnormal proteins from the ER lumen. Although the UPR is an intracellular defense mechanism to sustain cardiomyocyte viability and heart function, excessive activation initiates ER-dependent cardiomyocyte apoptosis. Myocardial ischemia/reperfusion (I/R) injury is a pathological process occurring during or after revascularization of ischemic myocardium. Several molecular mechanisms contribute to the pathogenesis of cardiac I/R injury. Due to the dual protective/degradative effects of ER stress on cardiomyocyte viability and function, it is of interest to understand the basic concepts, regulatory signals, and molecular processes involved in ER stress following myocardial I/R injury. In this review, therefore, we present recent findings related to the novel components of ER stress activation. The complex effects of ER stress and whether they mitigate or exacerbate myocardial I/R injury are summarized to serve as the basis for research into potential therapies for cardioprotection through control of ER homeostasis.

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“… A schematic showing the protein aggregation, endoplasmic reticulum (ER) stress response, and cell fate. Protein aggregation is a main feature of the neurodegenerative diseases [ 88 ]. Some of the proteins induced by ER stress have ferroptosis-inhibiting activities.…”

Section: Alternation Of Organelle Function Regarding Lipid Peroxidation and Protein Aggregationmentioning

confidence: 99%

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

Iuchi

Takai

Higuchi

2021

Biology

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Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases.

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The Endoplasmic Reticulum Stress/Unfolded Protein Response and Their Contributions to Parkinson’s Disease Physiopathology

Cited by 62 publications

References 213 publications

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

The Cross-Links of Endoplasmic Reticulum Stress, Autophagy, and Neurodegeneration in Parkinson’s Disease

Novel Insight into the Role of Endoplasmic Reticulum Stress in the Pathogenesis of Myocardial Ischemia‐Reperfusion Injury

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

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