Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 10, 2022

Neuronal death and inflammatory response are two common pathological hallmarks of acute central nervous system injury chronic degenerative disorders, both which closely related to cognitive motor dysfunction associated with various neurological diseases. Neurological diseases highly heterogeneous; however, they share a pathogenesis, that is, the aberrant accumulation misfolded/unfolded proteins within endoplasmic reticulum (ER). Fortunately, cell has intrinsic quality control mechanisms maintain proteostasis network, such as chaperone-mediated folding ER-associated degradation. However, when these fail, accumulate in ER lumen contribute stress. stress been implicated nearly all initiates unfolded protein restore proteostasis, if damage is irreversible, it elicits intracellular cascades inflammation. With growing appreciation functional association between improved understanding multiple underlying molecular mechanisms, pharmacological genetic targeting beginning emerge therapeutic approaches for

Language: Английский

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Empagliflozin alleviates endoplasmic reticulum stress and augments autophagy in rotenone-induced Parkinson's disease in rats: Targeting the GRP78/PERK/eIF2α/CHOP pathway and miR-211-5p

Chemico-Biological Interactions, Journal Year: 2022, Volume and Issue: 362, P. 110002 - 110002

Published: May 30, 2022

Language: Английский

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ERp57/PDIA3: new insight

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Feb. 2, 2022

Abstract The ERp57/PDIA3 protein is a pleiotropic member of the PDIs family and, although predominantly located in endoplasmic reticulum (ER), has indeed been found other cellular compartments, such as nucleus or cell membrane. an important research target considering it can be various subcellular locations. This involved many different physiological and pathological processes, our review describes new data on its functions summarizes some ligands identified PDIA3-specific inhibitors.

Language: Английский

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Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: March 28, 2022

Abstract Background The retina, as part of the central nervous system (CNS) with limited capacity for self-reparation and regeneration in mammals, is under cumulative environmental stress due to high-energy demands rapid protein turnover. These stressors disrupt cellular metabolic homeostasis, which, if not alleviated, can lead dysfunction cell death retinal neurons. One primary response highly conserved unfolded (UPR). UPR acts through three main signaling pathways an attempt restore homeostasis endoplasmic reticulum (ER) by various means, including but to, reducing translation, increasing protein-folding capacity, promoting misfolded degradation. Moreover, recent work has identified a novel function regulation metabolism mitochondrial function, disturbance which contributes neuronal degeneration dysfunction. role neurons during aging disease conditions age-related macular (AMD), retinitis pigmentosa (RP), glaucoma, diabetic retinopathy (DR) been explored over past two decades. Each their corresponding animal models provide distinct challenges unique opportunities gain better understanding maintenance health function. Method We performed extensive literature search on PubMed Google Scholar using following keywords: response, metabolism, ER stress, degeneration, aging, pigmentosa, retinopathy. Results conclusion summarize advances particular UPR, diseases, highlighting potential roles Further, we perspective promise targeting new therapeutic approach age- disease-related degeneration.

Language: Английский

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Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14498 - 14498

Published: Nov. 21, 2022

Mental disorders represent common brain diseases characterized by substantial impairments of social and cognitive functions. The neurobiological causes mechanisms psychopathologies still have not been definitively determined. Various forms proteinopathies, which include a disruption protein conformations the formation aggregates in tissues, may be possible cause behind development psychiatric disorders. Proteinopathies are known to main neurodegeneration, but much less attention is given role disorders' pathogenesis, such as depression schizophrenia. For this reason, aim review was discuss potential contribution illnesses psychopathologies. first part describes folding aggregation cell: endoplasmic reticulum stress, dysfunction chaperone proteins, altered mitochondrial function, impaired autophagy processes. second addresses proteins whose tissue has observed (amyloid, tau protein, α-synuclein, DISC-1, disbindin-1, CRMP1, SNAP25, TRIOBP, NPAS3, GluA1, FABP, ankyrin-G).

Language: Английский

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The endoplasmic reticulum stress and unfolded protein response in Alzheimer’s disease: A calcium dyshomeostasis perspective

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101914 - 101914

Published: March 21, 2023

Protein misfolding is prominent in early cellular pathology of Alzheimer's disease (AD), implicating pathophysiological significance endoplasmic reticulum stress/unfolded protein response (ER stress/UPR) and highlighting it as a target for drug development. Experimental data from animal AD models observations on human specimens are, however, inconsistent. ER stress associated UPR are readily observed vitro some model animals. In the brain, components markers well transducers at Braak stages III-VI with severe neuropathology neuronal death. The picture, further complicated by brain region- cell type-specificity AD-related pathology. Terms 'disturbed' or 'non-canonical' stress/UPR were used to describe discrepancies between experimental classic cascade. Here we discuss possible 'disturbing' 'interfering' factors which may modify pathogenesis. We focus dysregulation Ca2+ homeostasis, store-operated entry, interaction mitochondria. suggest that detailed study CNS type-specific alterations homeostasis deepen our understanding dysproteostasis.

Language: Английский

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ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1050 - 1050

Published: June 28, 2023

Endoplasmic reticulum (ER) stress and its adaptive mechanism, the unfolded protein response (UPR), are triggered by accumulation of misfolded proteins. During osteoclastogenesis, a large number active proteins synthesized. When an imbalance in folding process occurs, it causes osteoclasts to trigger UPR. This close association has led role UPR osteoclastogenesis being increasingly explored. In recent years, several studies have reported ER bone resorption. Here, we reviewed relevant literature discussed signaling cascade response, osteoclastogenesis-related pathways, resorption detail. It was found that signal (PERK, CHOP, IRE1-XBP1) promoted expression receptor activator nuclear factor-kappa B ligand (RANKL) osteoblasts indirectly enhanced osteoclastogenesis. IRE1 via promoting NF-κB, MAPK signaling, or release pro-inflammatory factors (IL-6, IL-1β, TNFα). CREBH osteoclast differentiation NFATc1 expression. The PERK pathway also through NF-κB autophagy, RANKL secretion from osteoblasts. However, salubrinal (an inhibitor eIF2α dephosphorylation upregulated p-eIF2α expression) directly inhibited suppressing Therefore, specific effects mechanisms p-PERK downstream on still need further experiments confirm. addition, exact ATF6 BiP required exploration. conclusion, our detailed systematic review provides some references for next step fully elucidate relationship between intending provide new insights treatment diseases caused over-differentiation, such as osteoporosis.

Language: Английский

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Neuromodulatory effect of vardenafil on aluminium chloride/d-galactose induced Alzheimer’s disease in rats: emphasis on amyloid-beta, p-tau, PI3K/Akt/p53 pathway, endoplasmic reticulum stress, and cellular senescence

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(5), P. 2653 - 2673

Published: July 17, 2023

Abstract Dysregulation of protein homeostasis, proteostasis, is a distinctive hallmark many neurodegenerative disorders and aging. Deleteriously, the accumulation aberrant proteins in Alzheimer’s disease (AD) accompanied with marked collapse proteostasis network. The current study explored potential therapeutic effect vardenafil (VAR), phosphodiesterase-5 inhibitor, AlCl 3 / d -galactose ( -gal)-induced AD rats its possible underlying mechanisms. impact VAR treatment on neurobehavioral function, hippocampal tissue architecture, activity cholinergic system main enzymes were assessed utilizing at doses 0.3 mg/kg 1 mg/kg. Additionally, expression level amyloid-beta phosphorylated tau hippocampus figured out. Accordingly, higher dose was selected to contemplate Intriguingly, elevated cyclic guanosine monophosphate averted repressed proteasome by -gal; hence, might alleviate burden toxic aggregates AD. In addition, substantial reduction activating transcription factor 6-mediated endoplasmic reticulum stress demonstrated treatment. Notably, counteracted -gal-induced depletion nuclear erythroid 2-related 2 level. Moreover, anti-senescence via ability restore balance redox circuit. modulation phosphatidylinositol-3-kinase/protein kinase B/p53 pathway kappa B level, key regulator senescence-associated secretory phenotype mediators release, also elucidated. Altogether, these findings insinuate benefits management. Graphic abstract

Language: Английский

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Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 123 - 123

Published: Jan. 9, 2024

The COVID-19 pandemic has brought to the forefront intricate relationship between SARS-CoV-2 and its impact on neurological complications, including potential links neurodegenerative processes, characterized by a dysfunction of protein quality control systems ER stress. This review article explores role systems, such as Unfolded Protein Response (UPR), Endoplasmic Reticulum-Associated Degradation (ERAD), Ubiquitin–Proteasome System (UPS), autophagy molecular chaperones, in infection. Our hypothesis suggests that produces stress exploits leading disruption proteostasis cannot be solved host cell. culminates cell death may represent link neurodegeneration.

Language: Английский

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The Misfolding Mystery: α-syn and the Pathogenesis of Parkinson's Disease

Neurochemistry International, Journal Year: 2024, Volume and Issue: 177, P. 105760 - 105760

Published: May 7, 2024

Language: Английский

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