Persistent diazinon induced neurotoxicity: The effect on inhibitory avoidance memory performance, amyloid precursor proteins, and TNF-α levels in the prefrontal cortex of rats DOI Creative Commons
Salva Afshari, Mehdi Sarailoo, Vahid Asghariazar

et al.

Human & Experimental Toxicology, Journal Year: 2024, Volume and Issue: 43

Published: Jan. 1, 2024

Introduction Organophosphate pesticides (Ops) like diazinon (DZN) have well-known neurotoxic effects and low-level chronic exposure has been linked to detrimental neurobehavioral impairments memory deficits. However, it’s not entirely clear how DZN-induced biological changes, particularly in the prefrontal cortex (PFC) contribute these effects. The purpose of this study is investigate impact DZN on inhibitory avoidance (IA) function, amyloid precursor expression (APP), proinflammatory tumor necrosis factor-α (TNF-α) levels rat cortex. Materials Methods Rats were divided into 4 groups recived 2 mg/kg for 5-days or 12-weeks two control same volume vehicle. IA was assesed using shuttle box apparatus. sacrificed PFC removed. Real-time PCR Western blotting used messure TNF-α, protein precursors gene levels. Results Our findings indicated that caused body weight loss a notable decline performance memory. Additionally, increased APP APLP2 PFC, while decreased Furthermore, gens PFC. TNF-α as result DZN, but dropped normal after administration, observation significant. Conclusion Taken together, low doses leads disturbances also alternations beta can be related risk Alzheimer’s disease.

Language: Английский

Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age DOI Creative Commons
Ashley Payne, Samuel N. Nahashon,

Equar Taka

et al.

Biomolecules, Journal Year: 2022, Volume and Issue: 12(3), P. 371 - 371

Published: Feb. 25, 2022

Alzheimer’s and Parkinson’s diseases are the two most common forms of neurodegenerative diseases. The exact etiology these disorders is not well known; however, environmental, molecular, genetic influences play a major role in pathogenesis Using disease (AD) as archetype, pathological findings include aggregation Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), cerebrovascular dysregulation. This review highlights neuroinflammatory neuroprotective epigallocatechin-3-gallate (EGCG): medicinal component green tea, known nutraceutical that has shown promise modulating AD progression due to its antioxidant, anti-inflammatory, anti-aging abilities. report also re-examines current literature provides innovative approaches for EGCG be used preventive measure alleviate other disorders.

Language: Английский

Citations

109
Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy DOI Open Access
Gian Marco Leone, Katia Mangano, Maria Cristina Petralia

et al.

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(4), P. 1630 - 1630

Published: Feb. 17, 2023

Due to the key role of tumor necrosis factor-alpha (TNF-α) in pathogenesis immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used clinical treatment autoimmune disorders. Currently, five anti-TNF-α drugs approved: infliximab, adalimumab, golimumab, certolizumab pegol etanercept. Anti-TNF-α biosimilars are also available for use. Here, we will review historical development as well present potential future applications therapies, which led major improvements patients with several such rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) chronic endogenous uveitis. Other therapeutic areas under evaluation, including viral infections, e.g., COVID-19, neuropsychiatric disorders certain forms cancer. The search biomarkers able predict responsiveness is discussed.

Language: Английский

Citations

82
Pathological changes within the cerebral vasculature in Alzheimer’s disease: New perspectives DOI Creative Commons
Robert A. Fisher, J. Scott Miners, Seth Love

et al.

Brain Pathology, Journal Year: 2022, Volume and Issue: 32(6)

Published: March 14, 2022

Abstract Cerebrovascular disease underpins vascular dementia (VaD), but structural and functional changes to the cerebral vasculature contribute pathology cognitive decline in Alzheimer's (AD). In this review, we discuss contribution of amyloid angiopathy non‐amyloid small vessel AD, accompanying density, maintenance remodelling vessels (including alterations composition function cerebrovascular basement membrane). We consider how abnormalities constituent cells neurovascular unit – particularly endothelial pericytes impairment blood‐brain barrier (BBB) impact on pathogenesis AD. also are likely impair Aβ clearance both intra‐periarteriolar drainage (IPAD) transport peptides across BBB, impaired coupling reduced blood flow relation metabolic demand increase amyloidogenic processing APP production Aβ. review vasoactive properties themselves, probable bi‐directional relationship between dysfunction accumulation Lastly, recent methodological advances transcriptomics imaging that have provided novel insights into assessment retina allow vivo detection early stages

Language: Английский

Citations

72
The relationship between inflammatory biomarkers and cognitive dysfunction in patients with schizophrenia: A systematic review and meta-analysis DOI
Saahithh Redddi Patlola, Gary Donohoe, Declan P. McKernan

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2022, Volume and Issue: 121, P. 110668 - 110668

Published: Oct. 23, 2022

Language: Английский

Citations

70
Inflammation in the pathogenesis of depression: a disorder of neuroimmune origin DOI Creative Commons
Myles Corrigan, Aoife M. O’Rourke, Barry Moran

et al.

Neuronal Signaling, Journal Year: 2023, Volume and Issue: 7(2)

Published: June 26, 2023

Abstract There are several hypotheses concerning the underlying pathophysiological mechanisms of major depression, which centre largely around adaptive changes in neuronal transmission and plasticity, neurogenesis, circuit regional connectivity. The immune endocrine systems commonly implicated driving these changes. An intricate interaction stress hormones, innate cells actions soluble mediators immunity within nervous system is described as being associated with symptoms depression. Bridging processes to neurotransmission signalling key cortical limbic brain circuits critical understanding depression a disorder neuroimmune origins. Emergent areas research include growing recognition system, advances neuroimaging techniques mechanistic insights gained from transgenic animals. Elucidation glial–neuronal interactions providing additional avenues into promising research, development clinically relevant disease models discovery novel therapies. This narrative review focuses on molecular cellular that influenced by inflammation stress. aim this provide an overview our current origin, focusing neuroendocrine dysregulation pathophysiology. Advances lie pursuit biomarkers, potential biomarker signatures improve clinical outcomes yet be fully realised. Further investigations expand panels including integration neuroimaging, utilising individual stratify patients more homogenous subpopulations targeting for new treatment approaches will help address unmet need.

Language: Английский

Citations

48
Roles of Cytokines in Alzheimer’s Disease DOI Open Access
Zilin Chen, Yekkuni L. Balachandran, Wai Po Chong

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5803 - 5803

Published: May 26, 2024

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic that plays pivotal role in pathogenesis progression Alzheimer’s disease (AD). Of particular focus are group signaling molecules facilitate communication among cells contribute to inflammation AD. Extensive research has shown dysregulated secretion certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, TNF-α) promotes neuroinflammation exacerbates neuronal damage However, anti-inflammatory (IL-2, IL-3, IL-33, IL-35) also secreted during AD onset progression, thereby preventing neuroinflammation. This review summarizes involvement pro- pathology discusses their therapeutic potential.

Language: Английский

Citations

17
Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases DOI Creative Commons
Wendy Balestri, Ruchi Sharma, Victor Allisson da Silva

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 23, 2024

Abstract Parkinson’s disease (PD) and Alzheimer’s (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, familial factors. These diseases have distinct pathologies symptoms that linked to specific cell populations in brain. Notably, immune system has been implicated both diseases, with a particular focus on dysfunction microglia, brain’s resident cells, contributing neuronal loss exacerbating symptoms. Researchers use models neuroimmune gain deeper understanding physiological biological aspects these how they progress. Several vitro vivo models, including 2D cultures animal utilized. Recently, advancements made optimizing existing developing 3D organ-on-a-chip systems, holding tremendous promise accurately mimicking intricate intracellular environment. As result, represent crucial breakthrough transformation current treatments for PD AD offering potential conducting long-term disease-based modeling therapeutic testing, reducing reliance significantly improving viability compared conventional models. The application research marks prosperous step forward, providing more realistic representation complex interactions within system. Ultimately, refined aim aid quest combat mitigate impact debilitating patients their families.

Language: Английский

Citations

16
TNF-α-dependent neuronal necroptosis regulated in Alzheimer's disease by coordination of RIPK1-p62 complex with autophagic UVRAG DOI Creative Commons
Chong Xu, Jialin Wu, Yiqun Wu

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 11(19), P. 9452 - 9469

Published: Jan. 1, 2021

Background: Neuronal death is a major hallmark of Alzheimer's disease (AD). Necroptosis, as programmed necrotic process, activated in AD. However, what signals and factors initiate necroptosis AD largely unknown. Methods: We examined the expression levels critical molecules necroptotic signaling pathway by immunohistochemistry (IHC) staining immunoblotting using brain tissues from patients mouse models APP/PS1 5×FAD. performed stereotaxic injection with recombinant TNF-α, anti-TNFR1 neutralizing antibody or AAV-mediated gene knockdown mice. For vitro studies, we used TNF-α combined zVAD-fmk Smac mimetic to establish neuronal utilized pharmacological molecular biological approaches study pathways. Results: find that dependent on upstream TNF-α/TNFR1 both cell cultures models. Upon stimulation, accumulated p62 recruits RIPK1 induces its self-oligomerization, activates downstream RIPK1/RIPK3/MLKL cascade, leading necroptosis. Ectopic accumulation caused impaired autophagy flux, which mediated UVRAG downregulation during TNF-α-promoted Notably, overexpression inhibits Conclusions: identify finely controlled regulation coordinated signaling, RIPK1/3 activity machinery. Strategies could fine-tune may bring promising therapeutics for

Language: Английский

Citations

87
Roles of Heme Oxygenase-1 in Neuroinflammation and Brain Disorders DOI Creative Commons
Yi‐Hsuan Wu, Hsi‐Lung Hsieh

Antioxidants, Journal Year: 2022, Volume and Issue: 11(5), P. 923 - 923

Published: May 8, 2022

The heme oxygenase (HO) system is believed to be a crucial mechanism for the nervous under stress conditions. HO degrades carbon monoxide, iron, and biliverdin. These degradation products are involved in modulating cellular redox homeostasis. first identified isoform of system, HO-1, an inducible protein that highly expressed peripheral organs barely detectable brain normal conditions, whereas HO-2 constitutive brain. Several lines evidence indicate HO-1 dysregulation associated with inflammation neurodegeneration, including Parkinson’s Alzheimer’s diseases. In this review, we summarize essential roles plays ensuring health molecular through which dysfunction leads neurodegenerative diseases disruption We also provide summary herbal medicines regulation expression explore current situation regarding remedies disorders.

Language: Английский

Citations

52
Role of pro-inflammatory cytokines in Alzheimer's disease and neuroprotective effects of pegylated self-assembled nanoscaffolds DOI Creative Commons
Varsha Rani,

Rinki Verma,

Krishan Kumar

et al.

Current Research in Pharmacology and Drug Discovery, Journal Year: 2022, Volume and Issue: 4, P. 100149 - 100149

Published: Dec. 20, 2022

Neurodegeneration and synaptic loss in Alzheimer's disease (AD) lead to impairment memory functions. Neuroinflammation causes activation of microglia astrocytes cells that locally systemically produces inflammatory cytokines which can serve as early diagnostic markers or therapeutic targets AD. Pro-inflammatory (Interleukins (IL-1β, IL-6 IL-10) tumor necrosis factor (TNF α)) levels were estimated serum, cerebral tissue, hepatic renal tissue treatment groups scopolamine-induced amnesia mice model using ELISA protocol. The results showed AD exhibited elevated IL1β, IL6, IL10 TNFα indicate contribution pro-inflammatory the progression A significant reduction concentration IL-10 TNF-α noticed animal group treated with marketed memantine tablet (Admenta), pure drug (MEMp), memantine-poly (lactic-co-glycolic acid) self-assembled nanoscaffolds (MEM-PLGA) SANs, Polyethylene Glycol coated [(PEG-MEM-PLGA) SANs] [(lactic-co-glycolic acid)] grafted Bone Marrow Derived Stem Cell ((PEG-MEM-PLGA) SANs-BMSc), whereas a high level was observed tissues normal induced emerging potential trigger either neurons survival after injury causing neurodegeneration cell apoptosis. Neuroregenerative stem helps proliferation neuronal thus improves cognition model.

Language: Английский

Citations

50