Guggulsterone selectively modulates STAT-3, mTOR, and PPAR-gamma signalling in a methylmercury-exposed experimental neurotoxicity: Evidence from CSF, blood plasma and brain samples DOI Creative Commons
Sumit Kumar, Sidharth Mehan, Zuber Khan

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Окт. 18, 2023

Abstract Amyotrophic lateral sclerosis (ALS) is a paralytic disease that damages the brain and spinal cord motor neurons. Several clinical preclinical studies have found methylmercury (MeHg + ) causes ALS. In ALS, -induced neurotoxicity manifests as oligodendrocyte destruction; myelin basic protein (MBP) deficiency leads to axonal death. ALS development has been connected an increase in signal transducer activator of transcription-3 (STAT-3), mammalian target rapamycin (mTOR), decrease peroxisome proliferator-activated receptor (PPAR)-gamma. Guggulsterone (GST), plant-derived chemical produced from Commiphorawhighitii resin, protect against by modulating these signalling pathways. Vitamin D 3 (VitD related precursor cells (OPC) damage, demyelination, white matter deterioration, which results neuron As result, primary goal this work was investigate therapeutic potential GST altering STAT-3, mTOR, PPAR-gamma levels MeHg -exposed experimental model adult rats. The GST30 60 mg/kg oral treatments significantly improved behavioral, motor, cognitive dysfunctions increased remyelination, proven Luxol Fast Blue stain (LFB), reduced neuroinflammation measured histological examinations. Furthermore, co-administration VitD3 exhibits moderate efficacy when administered combination with GST60. Our show protects neurons decreasing STAT-3 mTOR while increasing

Язык: Английский

Cdk5 and aberrant cell cycle activation at the core of neurodegeneration DOI Creative Commons
Raquel Requejo-Aguilar

Neural Regeneration Research, Год журнала: 2022, Номер 18(6), С. 1186 - 1186

Опубликована: Ноя. 26, 2022

Neurodegenerative diseases are caused by the progressive loss of specific neurons. The exact mechanisms action these unknown, and many studies have focused on pathways related to abnormal accumulation processing proteins, mitochondrial dysfunction, oxidative stress leading apoptotic death. However, a growing body evidence indicates that aberrant cell cycle re-entry plays major role in pathogenesis neurodegeneration. activation mature neurons could be promoted several signaling mechanisms, including c-Jun N-terminal kinases, p38 mitogen-activated protein kinase/extracellular signal-regulated kinase cascades; post-translational modifications such as Tau-phosphorylation; DNA damage response. In all events, implicated Cdk5, proline-directed serine/threonine kinase, seems responsible for cellular processes axon growth, neurotransmission, synaptic plasticity, neuronal migration, maintenance survival. under pathological conditions, Cdk5 dysregulation may lead post-mitotic Thus, hyperactivation, its physiologic activator p25, hyper-phosphorylates downstream substrates neurodegenerative diseases. This review summarizes factors stress, response, pathway disturbance, Ubiquitin proteasome malfunction contributing It also describes how linked greater or lesser extent with Cdk5. it offers global vision function cycle-related proteins focus this contributes development Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, Huntington's disease activation.

Язык: Английский

Процитировано

22
Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche DOI Creative Commons
Aleksandra Simiczyjew, Justyna Wądzyńska, Katarzyna Pietraszek‐Gremplewicz

и другие.

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Июль 22, 2023

Abstract Background One of the factors that affect progression melanoma is tumor microenvironment, which consists cellular elements, extracellular matrix, acidification, and a hypoxic state. Adipocytes are one types cell present in niche localized deepest layer skin. However, relationship between fat cells remains unclear. Methods We assessed influence on adipocytes using an indirect coculture system. estimated level cancer-associated adipocyte (CAA) markers through quantitative PCR analysis. The fibroblastic phenotype CAAs was confirmed by staining western blotting lipid content detection LipidSpot analysis Oil Red O. expression proteins involved synthesis, delipidation, metabolic processes were or Lactate secretion established Lactate-Glo™ assay. Proteins secreted identified cytokine angiogenesis arrays. proliferation cocultured with XTT Statistical performed one-way ANOVA followed Tukey’s test GraphPad Prism 7 software. Results Obtained decreased levels leptin, adiponectin, resistin, FABP4. presented features, such as similar proteolytic pattern to 3T3L1 fibroblasts increased vimentin TGFβRIII. Melanoma led reduction CAAs, possibly downregulation synthesis pathways (lower FADS, SC4MOL, FASN) enhancement lipolysis (higher phosphorylation ERK STAT3). higher IL6 SerpinE1 produced less CCL2, CXCL1, angiogenic molecules. also showed changes comprising lactate enhanced production glucose, lactate, ion transporters. In addition, observed following resulted rate cancer cells. Conclusions adipocytes, might be related delipidation synthesis. Fibroblast-like may reason for accelerated

Язык: Английский

Процитировано

11
Recent Advances in Biomolecular Patho-Mechanistic Pathways behind the Development and Progression of Diabetic Neuropathy DOI Creative Commons
Yashumati Ratan, Aishwarya Rajput, Ashutosh Pareek

и другие.

Biomedicines, Год журнала: 2024, Номер 12(7), С. 1390 - 1390

Опубликована: Июнь 23, 2024

Diabetic neuropathy (DN) is a neurodegenerative disorder that primarily characterized by distal sensory loss, reduced mobility, and foot ulcers may potentially lead to amputation. The multifaceted etiology of DN linked range inflammatory, vascular, metabolic, other factors. Chronic inflammation, endothelial dysfunction, oxidative stress are the three basic biological changes contribute development DN. Although our understanding intricacies has advanced significantly over past decade, distinctive mechanisms underlying condition still poorly understood, which be reason behind lack an effective treatment cure for present study delivers comprehensive highlights potential role several pathways molecular etiopathogenesis Moreover, Schwann cells satellite glial cells, as integral factors in pathogenesis DN, have been enlightened. This work will motivate allied research disciplines gain better analysis current state biomolecular essential effectively address every facet from prevention treatment.

Язык: Английский

Процитировано

4
Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders DOI

Manzar Khan,

Divya Choudhary,

Sidharth Mehan

и другие.

Neuropeptides, Год журнала: 2025, Номер 111, С. 102516 - 102516

Опубликована: Март 12, 2025

Язык: Английский

Процитировано

0
A molecular systems architecture of neuromuscular junction in amyotrophic lateral sclerosis DOI Creative Commons

V. A. Shiva Ayyadurai,

Prabhakar Deonikar,

Roger D. Kamm

и другие.

npj Systems Biology and Applications, Год журнала: 2025, Номер 11(1)

Опубликована: Март 17, 2025

A molecular systems architecture is presented for the neuromuscular junction (NMJ) in order to provide a framework organizing complexity of biomolecular interactions amyotrophic lateral sclerosis (ALS) using systematic literature review process. ALS fatal motor neuron disease characterized by progressive degeneration upper and lower neurons that supply voluntary muscles. The contains cells such as neurons, skeletal muscle cells, astrocytes, microglia, Schwann endothelial which are implicated pathogenesis ALS. This provides multi-layered understanding intra- inter-cellular microenvironment, may be utilized target identification, discovery single combination therapeutics, clinical strategies treat

Язык: Английский

Процитировано

0
Role of Fibroblast Growth Factors in Neurological Disorders: Insight into Therapeutic Approaches and Molecular Mechanisms DOI
Shubham Upadhayay,

Divya Soni,

Maanvi Dhureja

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 26, 2025

Язык: Английский

Процитировано

0
Molecular mechanisms and consequences of TDP-43 phosphorylation in neurodegeneration DOI Creative Commons

Elaine Kellett,

Adekunle T. Bademosi, Adam K. Walker

и другие.

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Май 8, 2025

Abstract Increased phosphorylation of TDP-43 is a pathological hallmark several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the regulation roles remain incompletely understood. A variety techniques have been utilized to understand phosphorylation, kinase/phosphatase manipulation, phosphomimic variants, genetic, physical, or chemical inducement in cell cultures animal models, via analyses post-mortem human tissues. These studies produced conflicting results: suggesting incongruously that may either drive disease progression serve neuroprotective role. In this review, we explore regulators putative kinases c-Abl, CDC7, CK1, CK2, IKKβ, p38α/MAPK14, MEK1, TTBK1, TTBK2, phosphatases PP1, PP2A, PP2B, disease. Building on recent studies, also examine consequences pathology, especially related mislocalisation, liquid–liquid phase separation, aggregation, neurotoxicity. By comparing findings from various review highlights both discrepancies unresolved aspects understanding phosphorylation. We propose role site context dependent, includes subcellular degradation. further suggest greater consideration normal functions be perturbed warranted. This synthesis aims build towards comprehensive complex pathogenesis neurodegeneration. Graphical subject by dephosphorylation phosphatases, which variably impacts protein localisation, neurotoxicity diseases.

Язык: Английский

Процитировано

0
Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders DOI
Abhishek Gupta, Sumedha Gupta, Sidharth Mehan

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Май 9, 2025

Язык: Английский

Процитировано

0
Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders DOI
Giuseppe Tridente, Ankit Jana,

Arnab Nath

и другие.

Elsevier eBooks, Год журнала: 2023, Номер unknown, С. 403 - 573

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

7
Ferroptosis-related gene MAPK3 is associated with the neurological outcome after cardiac arrest DOI Creative Commons

Hong xiang Hou,

Li Pang, Liang Zhao

и другие.

PLoS ONE, Год журнала: 2024, Номер 19(6), С. e0301647 - e0301647

Опубликована: Июнь 17, 2024

Background Neuronal ferroptosis is closely related to the disease of nervous system, and objective present study was recognize verify potential ferroptosis-related genes forecast neurological outcome after cardiac arrest. Methods Cardiac Arrest-related microarray datasets GSE29540 GSE92696 were downloaded from GEO batch normalization expression data performed using “sva” R package. GSE2 9540 analyzed identify DEGs. Venn diagram applied DEGs Subsequently, The Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis performed, PPI network screen hub genes. Receiver operating characteristic (ROC) curves adopted determine predictive value biomarkers, dataset further evaluate diagnostic efficacy biomarkers. We explore transcription factors miRNAs associated with “CIBERSORT” package utilized analyse proportion infiltrating immune cells. Finally, validated by a series experiments at cellular level. Results 112 overlapping obtained via intersecting these GO KEGG demonstrate that are mainly involved in response oxidative stress, ferroptosis, apoptosis, IL-17 signalling pathway, autophagy, toll-like receptor pathway. top 10 selected, including HIF1A, MAPK3, PPARA, IL1B, PTGS2, RELA, TLR4, KEAP1, SREBF1, SIRT6. Only MAPK3 upregulated both GAE92696. AUC values 0.654 0.850 respectively. result indicates hsa-miR-214-3p hsa-miR-483-5p can regulate MAPK3. positively correlated naive B cells, macrophages M0, activated dendritic cells negatively CD4 memory T CD8 Compared OGD4/R24 group, OGD4/R12 group had higher mRNA protein levels more severe ferroptosis. Conclusion In summary, gene could be used as biomarker predict Potential biological pathways provide novel insights into pathogenesis

Язык: Английский

Процитировано

2