keyword
https://read.qxmd.com/read/38530354/atrogin-1-promotes-muscle-homeostasis-by-regulating-levels-of-endoplasmic-reticulum-chaperone-bip
#1
JOURNAL ARTICLE
Avnika A Ruparelia, Margo Montandon, Jo Merriner, Cheng Huang, Siew Fen Lisa Wong, Carmen Sonntag, Justin P Hardee, Gordon S Lynch, Lee B Miles, Ashley Siegel, Thomas E Hall, Ralf B Schittenhelm, Peter D Currie
Skeletal muscle wasting results from numerous pathological conditions impacting both the musculoskeletal and nervous systems. A unifying feature of these pathologies is the upregulation of members of the E3 ubiquitin ligase family, resulting in increased proteolytic degradation of target proteins. Despite the critical role E3 ubiquitin ligases in regulating muscle mass, the specific proteins they target for degradation and the mechanisms by which they regulate skeletal muscle homeostasis remain ill-defined...
March 26, 2024: JCI Insight
https://read.qxmd.com/read/38527402/up-regulation-of-hsp90%C3%AE-in-hdm-induced-asthma-causes-pyroptosis-of-airway-epithelial-cells-by-activating-the-cgas-sting-er-stress-pathway
#2
JOURNAL ARTICLE
Haohua Huang, Yujie Qiao, Lanhe Chu, Cuiping Ye, Lishan Lin, Hua Liao, Xiaojing Meng, Fei Zou, Haijin Zhao, Mengchen Zou, Shaoxi Cai, Hangming Dong
Heat Shock protein 90 α (HSP90α), an main subtype of chaperone protein HSP90, involves important biological functions such as DNA damage repair, protein modification, innate immunity. However, the potential role of HSP90α in asthma occurrence and development is still unclear. This study aimed to elucidate the underlying mechanism of HSP90α in asthma by focusing on the cGAS-STING-Endoplasmic Reticulum stress pathway in inflammatory airway epithelial cell death (i.e., pyroptosis; inflammatory cell death)...
March 24, 2024: International Immunopharmacology
https://read.qxmd.com/read/38513326/multivalent-pyrrolidines-acting-as-pharmacological-chaperones-against-gaucher-disease
#3
JOURNAL ARTICLE
Marc Borie-Guichot, My Lan Tran, Virginie Garcia, Abdelouahd Oukhrib, Frédéric Rodriguez, Cédric-Olivier Turrin, Thierry Levade, Yves Génisson, Stéphanie Ballereau, Cécile Dehoux
A concise asymmetric synthesis of clickable enantiomeric pyrrolidines was achieved using Crabbé-Ma allenation. The synthesized iminosugars were grafted by copper-free strain-promoted alkyne-azide cycloaddition onto phosphorus dendrimers. The hexavalent and dodecavalent pyrrolidines were evaluated as β-glucocerebrosidase inhibitors. The level of inhibition suggests that monofluorocyclooctatriazole group may contribute to the affinity for the protein leading to potent multivalent inhibitors. Docking studies were carried out to rationalize these results...
March 16, 2024: Bioorganic Chemistry
https://read.qxmd.com/read/38508444/hspa9-mortalin-inhibition-disrupts-erythroid-maturation-through-a-tp53-dependent-mechanism-in-human-cd34-hematopoietic-progenitor-cells
#4
JOURNAL ARTICLE
Christopher Butler, Morgan Dunmire, Jaebok Choi, Gabor Szalai, Anissa Johnson, Wei Lei, Xin Chen, Liang Liu, Wei Li, Matthew J Walter, Tuoen Liu
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. They are the most common myeloid blood cancers in American adults. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Around 10%-25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes, including HSPA9...
March 18, 2024: Cell Stress & Chaperones
https://read.qxmd.com/read/38508313/the-structures-of-salt-inducible-kinase-3-in-complex-with-pharmacological-inhibitors-reveal-determinants-for-binding-and-selectivity
#5
JOURNAL ARTICLE
Linda Öster, Marie Castaldo, Emma de Vries, Fredrik Edfeldt, Nils Pemberton, Euan Gordon, Linda Cederblad, Helena Käck
The salt-inducible kinases (SIKs) 1-3, belonging to the AMPK-related kinase family, serve as master regulators orchestrating a diverse set of physiological processes such as metabolism, bone formation, immune response, oncogenesis and cardiac rhythm. Owing to its key regulatory role, the SIK kinases have emerged as compelling targets for pharmacological intervention across a diverse set of indications. Therefore, there is interest in developing SIK inhibitors with defined selectivity profiles both to further dissect the downstream biology and for treating disease...
March 18, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38495093/ac-sdkp-attenuates-er-stress-stimulated-collagen-production-in-cardiac-fibroblasts-by-inhibiting-chop-mediated-nf-%C3%AE%C2%BAb-expression
#6
JOURNAL ARTICLE
Hamid Suhail, Hongmei Peng, Khalid Matrougui, Nour-Eddine Rhaleb
Inflammation and cardiac fibrosis are prevalent pathophysiologic conditions associated with hypertension, cardiac remodeling, and heart failure. Endoplasmic reticulum (ER) stress triggers the cells to activate unfolded protein responses (UPRs) and upregulate the ER stress chaperon, enzymes, and downstream transcription factors to restore normal ER function. The mechanisms that link ER stress-induced UPRs upregulation and NF-κB activation that results in cardiac inflammation and collagen production remain elusive...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38490517/novel-mechanisms-involved-in-leptin-sensitization-in-obesity
#7
REVIEW
Veronica Pena-Leon, Raquel Perez-Lois, Maria Villalon, Eva Prida, Diego Muñoz-Moreno, Johan Fernø, Mar Quiñones, Omar Al-Massadi, Luisa M Seoane
Leptin is a hormone that is secreted by adipocytes in proportion to adipose tissue size, and that informs the brain about the energy status of the body. Leptin acts through its receptor LepRb, expressed mainly in the hypothalamus, and induces a negative energy balance by potent inhibition of feeding and activation of energy expenditure. These actions have led to huge expectations for the development of therapeutic targets for metabolic complications based on leptin-derived compounds. However, the majority of patients with obesity presents elevated leptin production, suggesting that in this setting leptin is ineffective in the regulation of energy balance...
March 13, 2024: Biochemical Pharmacology
https://read.qxmd.com/read/38485341/activation-of-%C3%AF-1-receptor-mitigates-estrogen-withdrawal-induced-anxiety-depressive-like-behavior-in-mice-via-restoration-of-gaba-glutamate-signaling-and-neuroplasticity-in-the-hippocampus
#8
JOURNAL ARTICLE
Peng Ren, Jing-Ya Wang, Hong-Lei Chen, Yue Wang, Lin-Yu Cui, Jing-Yao Duan, Wen-Zhi Guo, Yong-Qi Zhao, Yun-Feng Li
Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed...
April 2024: Journal of Pharmacological Sciences
https://read.qxmd.com/read/38485044/roles-of-heat-shock-protein-a12a-in-the-development-of-diabetic-cardiomyopathy
#9
JOURNAL ARTICLE
Yunxiao Jia, Yunhao Yu, Chenxi Gao, Yuehua Li, Chuanfu Li, Zhengnian Ding, Qiuyue Kong, Li Liu
Long-term hyperglycemia can lead to diabetic cardiomyopathy (DCM), a main lethal complication of diabetes. However, the mechanisms underlying DCM development have not been fully elucidated. Heat shock protein A12A (HSPA12A) is the atypic member of HSP70 family. In the present study, we found that the expression of HSPA12A was upregulated in hearts of mice with streptozotocin (STZ)-induced diabetes, while ablation of HSPA12A improved cardiac systolic and diastolic dysfunction and increased cumulative survival of diabetic mice...
March 12, 2024: Cell Stress & Chaperones
https://read.qxmd.com/read/38485043/role-of-mitochondria-in-doxorubicin-mediated-cardiotoxicity-from-molecular-mechanisms-to-therapeutic-strategies
#10
REVIEW
Tianen Wang, Guoli Xing, Tong Fu, Yanchun Ma, Qi Wang, Shuxiang Zhang, Xing Chang, Ying Tong
This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect...
March 12, 2024: Cell Stress & Chaperones
https://read.qxmd.com/read/38458414/exploring-ligand-interactions-with-human-phosphomannomutases-using-recombinant-bacterial-thermal-shift-assay-and-biochemical-validation
#11
JOURNAL ARTICLE
Maria Monticelli, Bruno Hay Mele, Demi Marie Wright, Simone Guerriero, Giuseppina Andreotti, Maria Vittoria Cubellis
PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches. We used Recombinant Bacterial Thermal Shift Assay to assess the binding of a substrate analog to phosphomannomutase-2 and the specific binding to phosphomannomutase-1 of an FDA-approved drug - clodronate...
March 6, 2024: Biochimie
https://read.qxmd.com/read/38449709/heat-shock-protein-paradigms-in-cancer-progression-future-therapeutic-perspectives
#12
REVIEW
Y Mohammed Tausif, Dithu Thekkekkara, Thummuru Ekshita Sai, Vaishnavi Jahagirdar, H R Arjun, S K Meheronnisha, Amrita Babu, Aniruddha Banerjee
Heat-shock proteins (HSPs), also known as stress proteins, are ubiquitously present in all forms of life. They play pivotal roles in protein folding and unfolding, the formation of multiprotein complexes, the transportation and sorting of proteins into their designated subcellular compartments, the regulation of the cell cycle, and signalling processes. These HSPs encompass HSP27, HSP40, HSP70, HSP60, and HSP90, each contributing to various cellular functions. In the context of cancer, HSPs exert influence by either inhibiting or activating diverse signalling pathways, thereby impacting growth, differentiation, and cell division...
April 2024: 3 Biotech
https://read.qxmd.com/read/38441084/recent-developments-of-hsp90-inhibitors-an-updated-patent-review-2020-present
#13
REVIEW
Jianfeng Liu, Huangliang Shu, Qinxin Xia, Qidong You, Lei Wang
INTRODUCTION: The 90-kDa heat shock protein (HSP90) functions as a molecular chaperone, it assumes a significant role in diseases such as cancer, inflammation, neurodegeneration, and infection. Therefore, the research and development of HSP90 inhibitors have garnered considerable attention. AREAS COVERED: The primary references source for this review is patents obtained from Scifinder, encompassing patents on HSP90 inhibitors from the period of 2020 to 2023.This review includes a thorough analysis of their structural attributes, pharmacological properties, and potential clinical utilities...
March 5, 2024: Expert Opinion on Therapeutic Patents
https://read.qxmd.com/read/38432923/-toward-the-complete-understanding-of-the-pathogenic-mechanism-of-clioquinol-induced-subacute-myelo-optic-neuropathy-smon
#14
JOURNAL ARTICLE
Masato Katsuyama
Clioquinol was extensively used as an amebicide to treat indigestion and diarrhea in the mid-1900s. However, it was withdrawn from the market in Japan because its use was epidemiologically linked to an increase in the incidence of subacute myelo-optic neuropathy (SMON). SMON is characterized by the subacute onset of sensory and motor disturbances in the lower extremities with occasional visual impairments, which are preceded by abdominal symptoms. Although pathological studies demonstrated axonopathy of the spinal cord and optic nerves, the underlying mechanisms of clioquinol toxicity have not been elucidated in detail...
2024: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://read.qxmd.com/read/38423952/protective-role-of-the-hsp90-inhibitor-sta-9090-in-lungs-of-sars-cov-2-infected-syrian-golden-hamsters
#15
JOURNAL ARTICLE
Luiz Gustavo Teixeira Alves, Morris Baumgardt, Christine Langner, Mara Fischer, Julia Maria Adler, Judith Bushe, Theresa Catharina Firsching, Guido Mastrobuoni, Jenny Grobe, Katja Hoenzke, Stefan Kempa, Achim Dieter Gruber, Andreas Christian Hocke, Jakob Trimpert, Emanuel Wyler, Markus Landthaler
INTRODUCTION: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication...
February 29, 2024: BMJ Open Respiratory Research
https://read.qxmd.com/read/38416826/hsp90%C3%AE-controls-nlrp3-autoactivation
#16
JOURNAL ARTICLE
Lotte Spel, Cyrielle Hou, Katerina Theodoropoulou, Léa Zaffalon, Zhuo Wang, Arinna Bertoni, Stefano Volpi, Michaël Hofer, Marco Gattorno, Fabio Martinon
Gain-of-function mutations in NLRP3 are linked to cryopyrin-associated periodic syndromes (CAPS). Although NLRP3 autoinflammasome assembly triggers inflammatory cytokine release, its activation mechanisms are not fully understood. Our study used a functional genetic approach to identify regulators of NLRP3 inflammasome formation. We identified the HSP90β-SGT1 chaperone complex as crucial for autoinflammasome activation in CAPS. A deficiency in HSP90β, but not in HSP90α, impaired the formation of ASC specks without affecting the priming and expression of inflammasome components...
March 2024: Science Advances
https://read.qxmd.com/read/38415587/sex-dependent-changes-to-the-intestinal-and-hepatic-abundance-of-drug-transporters-and-metabolizing-enzymes-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#17
JOURNAL ARTICLE
Liam M Koehn, Joel R Steele, Ralf B Schittenhelm, Bradley J Turner, Joseph A Nicolazzo
Amyotrophic lateral sclerosis (ALS) is characterized by death and dysfunction of motor neurons that result in a rapidly progressing loss of motor function. While there are some data on alterations at the blood-brain barrier (BBB) in ALS and their potential impact on CNS trafficking of drugs, little is reported on the impact of this disease on the expression of drug-handling proteins in the small intestine and liver. This may impact the dosing of the many medicines that individuals with ALS are prescribed. In the present study, a proteomic evaluation was performed on small intestine and liver samples from postnatal day 120 SOD1G93A mice (a model of familial ALS that harbors a human mutant form of superoxide dismutase 1) and wild-type (WT) littermates ( n = 7/genotype/sex)...
February 28, 2024: Molecular Pharmaceutics
https://read.qxmd.com/read/38414738/exploring-the-efficacy-and-safety-of-ambroxol-in-gaucher-disease-an-overview-of-clinical-studies
#18
REVIEW
Feda E Mohamed, Fatma Al-Jasmi
Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of different GBA1 genotypes...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38402623/sepn1-related-myopathy-depends-on-the-oxidoreductase-ero1a-and-is-druggable-with-the-chemical-chaperone-tudca
#19
JOURNAL ARTICLE
Serena Germani, Andrew Tri Van Ho, Alessandro Cherubini, Ersilia Varone, Alexander Chernorudskiy, Giorgia Maria Renna, Stefano Fumagalli, Marco Gobbi, Jacopo Lucchetti, Marco Bolis, Luca Guarrera, Ilaria Craparotta, Giorgia Rastelli, Giorgia Piccoli, Cosimo de Napoli, Leonardo Nogara, Elena Poggio, Marisa Brini, Angela Cattaneo, Angela Bachi, Thomas Simmen, Tito Calì, Susana Quijano-Roy, Simona Boncompagni, Bert Blaauw, Ana Ferreiro, Ester Zito
Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and the ER-stress-induced oxidoreductase ERO1A. SEPN1 and ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved in the redox regulation of proteins. ERO1A depletion in SEPN1 knockout cells restores ER redox, re-equilibrates short-range MAMs, and rescues mitochondrial bioenergetics. ERO1A knockout in a mouse background of SEPN1 loss blunts ER stress and improves multiple MAM functions, including Ca2+ levels and bioenergetics, thus reversing diaphragmatic weakness...
February 19, 2024: Cell reports medicine
https://read.qxmd.com/read/38387701/implication-of-rac1-gtpase-in-molecular-and-cellular-mitochondrial-functions
#20
REVIEW
Christian Bailly, Claire Degand, William Laine, Vincent Sauzeau, Jérôme Kluza
Rac1 is a member of the Rho GTPase family which plays major roles in cell mobility, polarity and migration, as a fundamental regulator of actin cytoskeleton. Signal transduction by Rac1 occurs through interaction with multiple effector proteins, and its activity is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The small protein is mainly anchored to the inner side of the plasma membrane but it can be found in endocellular compartments, notably endosomes and cell nuclei...
February 20, 2024: Life Sciences
keyword
keyword
76513
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.