Roles of XBP1s in Transcriptional Regulation of Target Genes

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 791 - 791

Published: July 8, 2021

The spliced form of X-box binding protein 1 (XBP1s) is an active transcription factor that plays a vital role in the unfolded response (UPR). Under endoplasmic reticulum (ER) stress, unspliced Xbp1 mRNA cleaved by activated stress sensor IRE1α and converted to mature encoding XBP1 (XBP1s). Translated XBP1s migrates nucleus regulates transcriptional programs UPR target genes ER molecular chaperones, folding enzymes, ER-associated degradation (ERAD) components decrease stress. Moreover, studies have shown diverse are involved lipid glucose metabolism immune responses. Therefore, has been considered important therapeutic studying various diseases, including cancer, diabetes, autoimmune inflammatory diseases. several unique mechanisms regulate different interacting with other proteins modulate their activity. Although recent discovered numerous via genome-wide analyses, how remains unclear. This review discusses roles regulation. More in-depth knowledge regulatory future will help develop new targets for each disease.

Language: Английский

---

Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7698 - 7698

Published: Oct. 18, 2020

Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology these diseases is linked with mitochondrial dysfunction. In this review, we discuss current knowledge concerning effects HHcy on homeostasis, energy metabolism, apoptotic pathway, dynamics. The recent studies suggest interaction between Hcy mitochondria complex, reactive oxygen species (ROS) are possible mediators effects. We focus mechanisms contributing to HHcy-associated oxidative stress, such as sources ROS generation alterations antioxidant defense resulting from altered gene expression post-translational modifications proteins. Moreover, some findings suggesting may have beneficial homeostasis defense. A better understanding complex through which affects functions could contribute development more specific therapeutic strategies targeted at disorders.

Language: Английский

---

Therapeutic inhibition of ferroptosis in neurodegenerative disease

Trends in Pharmacological Sciences, Journal Year: 2023, Volume and Issue: 44(10), P. 674 - 688

Published: Aug. 30, 2023

Language: Английский

---

The neuroprotective effects of targeting key factors of neuronal cell death in neurodegenerative diseases: The role of ER stress, oxidative stress, and neuroinflammation

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 6, 2023

Neuronal loss is one of the striking causes various central nervous system (CNS) disorders, including major neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and Amyotrophic lateral sclerosis (ALS). Although these diseases have different features clinical manifestations, they share some common mechanisms pathology. Progressive regional neurons in patients responsible for motor, memory, cognitive dysfunctions, leading to disabilities death. cell death linked pathways conditions. Protein misfolding aggregation, mitochondrial dysfunction, generation reactive oxygen species (ROS), activation innate immune response are most critical hallmarks diseases. Thus, endoplasmic reticulum (ER) stress, oxidative neuroinflammation pathological factors neuronal Even though exact not fully discovered, notable role mentioned well known. On this basis, researchers been prompted investigate neuroprotective effects targeting underlying determine a promising therapeutic approach treatment. This review provides an overview ER death, mainly discussing or molecules involved factors.

Language: Английский

---

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: March 20, 2024

Abstract The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads stress (ER stress). As ER ensues, protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, kinase R-like kinase, activating transcription factor 6 promptly activates enhance ER’s protein-folding capacity restore homeostasis. However, prolonged levels propels UPR towards cellular demise subsequent inflammatory cascade, contributing development human diseases, including cancer, neurodegenerative disorders, diabetes. Notably, increased expression all pathways has been observed in these pathologies, reduction molecule correlates with decreased proliferation disease-associated target cells. Consequently, therapeutic strategies targeting stress-related interventions have attracted significant research interest. In this review, we elucidate critical role metabolic, offering novel approaches for conditions.

Language: Английский

---

Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis in the Pathology of Alzheimer’s Disease

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 82(2), P. 457 - 477

Published: March 12, 2024

Language: Английский

---

Endoplasmic reticulum stress and unfolded protein response: Roles in skeletal muscle atrophy

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 234, P. 116799 - 116799

Published: Feb. 12, 2025

Language: Английский

---

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

Frontiers in Aging Neuroscience, Journal Year: 2021, Volume and Issue: 13

Published: June 3, 2021

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

Language: Английский

---

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1171 - 1171

Published: Jan. 25, 2021

Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. exists various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate isoenzyme type M2 (PKM2) controls cell progression survival regulation signaling pathways. In cancer cells, dimer form PKM2 predominates plays an integral role metabolism. This predominance inactive dimeric promotes accumulation phosphometabolites, allowing cells to engage high levels synthetic processing enhance their proliferative capacity. has been recognized for its regulating gene expression transcription factors critical health disease. enables exert profound regulatory effects promote metabolism, proliferation, migration. addition cancer, regulates aspects essential cellular homeostasis non-cancer tissues and, some cases, tissue-specific pathways diseases. pursuit understanding roles PKM2, investigations targeting such as kidney, liver, adipose, pancreas have conducted. Findings from these studies our diseases beyond cancer. Therefore, there substantial interest modulation potential therapeutic target treatment multiple conditions. Indeed, vast plethora research focused on identifying strategies PKM2. Recently, microRNAs, long non-coding RNAs (lncRNAs), circular (circRNAs) gathered increasing interest. Thus, goal this review highlight recent advancements research, with focus microRNAs lncRNAs subsequent physiological significance.

Language: Английский

---

Emerging roles of N-linked glycosylation in brain physiology and disorders

Trends in Endocrinology and Metabolism, Journal Year: 2021, Volume and Issue: 32(12), P. 980 - 993

Published: Oct. 29, 2021

Language: Английский

---