The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids

Zarneshan, Seyede Nazanin; Fakhri, Sajad; Moradi, Seyed Zachariah; Echeverría, Javier

doi:10.1016/j.phymed.2023.154686

Cited by 19 publications

(9 citation statements)

References 301 publications

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“…Cluster 1 showed a higher abundance of B cell memory, T cell CD8, NK cell activation, and mast cell quiescence. Additionally, DEOSGs of cluster 1 are enriched in the JAK/STAT pathway, which plays a crucial role in promoting neuroinflammation in neurodegenerative diseases like AD [ 20 ]. This pathway initiates innate immunity, coordinates adaptive immune mechanisms, and ultimately suppresses neuroinflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Novel diagnostic biomarkers of oxidative stress, immunological characterization and experimental validation in Alzheimer’s disease

Hu,

Mo,

Jihang

et al. 2023

Aging

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Alzheimer’s disease (AD) is a neurodegenerative condition causing cognitive decline. Oxidative stress (OS) is believed to contribute to neuronal death and dysfunction in AD. We conducted a study to identify differentially expressed OS-related genes (DEOSGs) through bioinformatics analysis and experimental validation, aiming to develop a diagnostic model for AD. We analyzed the GSE33000 dataset to identify OS regulator expression profiles and create molecular clusters (C1 and C2) associated with immune cell infiltration using 310 AD samples. Cluster analysis revealed significant heterogeneity in immune infiltration. The ‘WGCNA’ algorithm identified cluster-specific and disease-specific differentially expressed genes (DGEs). Four machine learning models (random forest (RF), support vector machine (SVM), generalized linear model (GLM) and extreme gradient boosting (XGB)) were compared, with GLM performing the best (AUC = 0.812). Five DEOSGs (NFKBIA, PLCE1, CLIC1, SLCO4A1, TRAF3IP2) were identified based on the GLM model. AD subtype prediction accuracy was validated using nomograms and calibration curves. External datasets (GSE122063 and GSE106241) confirmed the expression levels and clinical significance of important genes. Experimental validation through RT-qPCR showed increased expression of NFKBIA, CLIC1, SLCO4A1, TRAF3IP2, and decreased expression of PLCE1 in the temporal cortex of AD mice. This study provides insights for AD research and treatment, particularly focusing on the five model-related DEOSGs.

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Section: Discussionmentioning

confidence: 99%

Novel diagnostic biomarkers of oxidative stress, immunological characterization and experimental validation in Alzheimer’s disease

Hu,

Mo,

Jihang

et al. 2023

Aging

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“…Quercetin derivatives, such as C3 and C4OH glycoside derivatives, have a lower H + donating capacity. In addition, the reducing potential of the C3OH derivatives of quercetin is higher compared to its aglycone form [ 18 , 19 ].…”

Section: Quercetin Particularitiesmentioning

confidence: 99%

Quercetin, a Flavonoid with Great Pharmacological Capacity

Carrillo-Martinez,

Flores-Hernández,

Salazar-Montes

et al. 2024

Molecules

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Quercetin is a flavonoid with a low molecular weight that belongs to the human diet’s phenolic phytochemicals and nonenergy constituents. Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC), which act as reducing agents by chelating transition-metal ions. Its structure has five functional hydroxyl groups, which work as electron donors and are responsible for capturing free radicals. In addition to its antioxidant capacity, different pharmacological properties of quercetin have been described, such as carcinostatic properties; antiviral, antihypertensive, and anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis; these are developed in this review.

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“…Stimulating STAT1 and STAT3 activity in patients with PD causes a dramatic rise in Th1 and Th17 levels [130]. Recruitment of inflammatory cytokines such as IFN-γ, TNF-α, IL-1β, and IL-23 through the JAK/STAT activation is crucial in inducing ROS, nitric oxide species (NOS), and the decline of DA neurons [131].…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson’s Disease?

Xue,

Tao,

Wang

et al. 2024

IJMS

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Parkinson’s disease (PD) is a common neurodegenerative disorder with a complicated etiology and pathogenesis. α-Synuclein aggregation, dopaminergic (DA) neuron loss, mitochondrial injury, oxidative stress, and inflammation are involved in the process of PD. Neuroinflammation has been recognized as a key element in the initiation and progression of PD. In this review, we summarize the inflammatory response and pathogenic mechanisms of PD. Additionally, we describe the potential anti-inflammatory therapies, including nod-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome inhibition, nuclear factor κB (NF-κB) inhibition, microglia inhibition, astrocyte inhibition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition, the peroxisome proliferator-activated receptor γ (PPARγ) agonist, targeting the mitogen-activated protein kinase (MAPK) pathway, targeting the adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway, targeting α-synuclein, targeting miRNA, acupuncture, and exercise. The review focuses on inflammation and will help in designing new prevention strategies for PD.

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The pivotal role of JAK/STAT and IRS/PI3K signaling pathways in neurodegenerative diseases: Mechanistic approaches to polyphenols and alkaloids

Cited by 19 publications

References 301 publications

Novel diagnostic biomarkers of oxidative stress, immunological characterization and experimental validation in Alzheimer’s disease

Novel diagnostic biomarkers of oxidative stress, immunological characterization and experimental validation in Alzheimer’s disease

Quercetin, a Flavonoid with Great Pharmacological Capacity

What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson’s Disease?

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