Neutralization of IL‐17 rescues amyloid‐β‐induced neuroinflammation and memory impairment DOI Open Access
Claudia Cristiano, Floriana Volpicelli, Pellegrino Lippiello

et al.

British Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 176(18), P. 3544 - 3557

Published: Jan. 24, 2019

Background and purpose Alzheimer's disease (AD) is a common neurodegenerative characterized by neuroinflammatory state, to date, there no cure its treatment represents large unmet clinical need. The involvement of Th17 cells in the pathogenesis AD‐related neuroinflammation has been reported several studies. However, role cytokine, IL‐17 not well addressed. Herein, we investigate effects neutralizing antibody (IL‐17Ab) injected i.c.v. or intranasal (IN) routes on amyloid‐β (Aβ)‐induced memory impairment mice. Experimental approach Aβ 1–42 was into cerebral ventricles adult CD1 These mice received IL‐17Ab via either at 1 h prior injection IN 5 12 days after injection. After 7 14 administration, evaluated olfactory, spatial working performed biochemical analyses whole brain specific areas. Key results Pretreatment with IL‐17Ab, given, i.c.v., markedly reduced ‐induced neurodegeneration, improved function, prevented increase pro‐inflammatory mediators dose‐dependent manner days. Similarly, double administration decline, levels proinflammatory cytokines. Conclusion implications findings suggest that behavioural symptoms induced Aβ. efficacy reducing neurodegeneration points possible future therapeutic patients AD. Linked Articles This article part themed section Therapeutics for Dementia Disease: New Directions Precision Medicine. To view other articles this visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

Language: Английский

Neuroinflammation and the Kynurenine Pathway in CNS Disease: Molecular Mechanisms and Therapeutic Implications DOI Creative Commons
Mustafa N. Mithaiwala, Danielle Santana‐Coelho, Grace A. Porter

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1548 - 1548

Published: June 19, 2021

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around globe. The development therapeutic strategies for CNS conditions has suffered due to poor understanding underlying pathologies that manifest them. Understanding common etiological origins at cellular molecular level is essential enhance efficacious targeted treatment options. Over years, neuroinflammation been posited as link between multiple neurological, neurodegenerative neuropsychiatric disorders. Processes precipitate neuroinflammatory including genetics, infections, physical injury psychosocial factors, like stress trauma, closely dysregulation in kynurenine pathway (KP) tryptophan metabolism possible pathophysiological factor 'fuel fire' diseases. In this study, we aim review emerging evidence provide mechanistic insights different disorders, KP. We thorough overview branches KP pertinent disease pathology have implications selected strategies.

Language: Английский

Citations

119
Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis? DOI Creative Commons
Feixue Wang, Jiandong Wang, Ying Shen

et al.

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: March 22, 2022

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited brain as we age. Early studies found overload directly proportional to cognitive decline Alzheimer’s disease (AD). Amyloid precursor protein (APP) and tau protein, both which are related AD pathogenesis, associated with metabolism. A variety metabolism-related proteins have been be abnormally expressed brains patients mouse models, resulting deposition promoting progression. β (Aβ) hyperphosphorylated tau, two pathological hallmarks AD, can also promote brain, forming vicious cycle development-iron deposition. subsequent ferroptosis has potential mechanism underlying neuronal loss neurodegenerative diseases. chelators, antioxidants hepcidin were useful for treating represents an important direction treatment research drug development future. The review explored deep connection between dysregulation discussed new hypothesis dyshomeostasis ferroptosis, summarized therapeutics capable targeting iron, expectation draw more attention corresponding development.

Language: Английский

Citations

105
Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review DOI Open Access
Bartosz Twarowski, Mariola Herbet

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6518 - 6518

Published: March 30, 2023

Alzheimer’s disease is one of the most commonly diagnosed cases senile dementia in world. It an incurable process, often leading to death. This multifactorial, and factor this inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms disease, contributing progression, also directly underlie AD. Although much has been established about processes pathogenesis AD, many aspects remain unexplained. The work devoted particular pathomechanism inflammation its role diagnosis treatment. An in-depth detailed understanding neuroinflammation help development diagnostic methods for early contribute new therapeutic strategies disease.

Language: Английский

Citations

105
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease DOI Open Access

Nour F. Al-Ghraiybah,

Junwei Wang, Amer E. Alkhalifa

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572

Published: Sept. 12, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target

Language: Английский

Citations

92
Neuroinflammation: A Potential Risk for Dementia DOI Open Access
Md Afroz Ahmad, Ozaifa Kareem,

Mohammad Khushtar

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 616 - 616

Published: Jan. 6, 2022

Dementia is a neurodegenerative condition that considered major factor contributing to cognitive decline reduces independent function. Pathophysiological pathways are not well defined for diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in brain toward their pathology. Microglia central nervous system (CNS) principal components brain’s immune defence and can detect harmful or external pathogens. When stimulated, cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, nitrogen species order preserve cell’s microenvironment. These markers include cytokines IL-1, IL-6, TNFα chemokines CCR3 CCL2 CCR5. Microglial may produce prolonged response that, some circumstances, indicated promotion diseases. The present review focused on involvement microglial cell activation throughout conditions link between dementia.

Language: Английский

Citations

90
Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease DOI Creative Commons
Minghui Wang, Hu Zhang, Jiling Liang

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 19, 2023

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disease, with the characteristics of neurofibrillary tangle (NFT) and senile plaque (SP) formation. Although great progresses have been made in clinical trials based on relevant hypotheses, these studies are also accompanied by emergence toxic side effects, it an urgent task to explore underlying mechanisms for benefits prevent treat AD. Herein, animal experiments few trials, neuroinflammation AD characterized long-term activation pro-inflammatory microglia NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasomes. Damaged signals from periphery within brain continuously activate microglia, thus resulting constant source inflammatory responses. The response exacerbates endoplasmic reticulum oxidative stress which triggers microglia-dependent immune responses, ultimately leading occurrence deterioration In this review, we systematically summarized sorted out that exercise ameliorates directly indirectly regulating central nervous system promoting hippocampal neurogenesis provide new direction exploring activity

Language: Английский

Citations

83
The impact of loneliness and social isolation on the development of cognitive decline and Alzheimer’s Disease DOI Creative Commons
Yi Ren,

Aisouda Savadlou,

Soobin Park

et al.

Frontiers in Neuroendocrinology, Journal Year: 2023, Volume and Issue: 69, P. 101061 - 101061

Published: Feb. 8, 2023

Alzheimer's Disease (AD) is the leading cause of dementia, observed at a higher incidence in women compared with men. Treatments aimed improving pathology AD remain ineffective to stop disease progression. This makes detection early intervention strategies reduce future risk extremely important. Isolation and loneliness have been identified among major factors for AD. The increasing prevalence both emphasizes urgent need understand this association inform treatment. Here we present comprehensive review clinical preclinical studies that investigated social isolation as We discuss understanding mechanisms how exacerbates cognitive impairment focus on sex differences will shed light underlying regarding factor develop effective prevention or treatment strategies.

Language: Английский

Citations

57
Burden of Illness in People with Alzheimer’s Disease: A Systematic Review of Epidemiology, Comorbidities and Mortality DOI
Krista L. Lanctôt,

Julie Hviid Hahn‐Pedersen,

C Eichinger

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Language: Английский

Citations

50
Exercise therapy to prevent and treat Alzheimer’s disease DOI Creative Commons
Hamed Alizadeh Pahlavani

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Aug. 4, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition amyloid beta (Aβ) phosphorylated tau, age, mitochondrial defects, neuroinflammation, decreased synaptic connections, nerve growth factors (NGF). While animals moderate-intensity exercise restores hippocampal amygdala through levels p-AKT, p-TrkB, p-PKC Aβ, tau phosphorylation, precursor proteins (APP) AD. Aerobic (with an intensity 50–75% VO2 max) prevents volume reduction, spatial learning reduction increasing flexibility. Exercise training induces binding brain-derived neurotrophic factor (BDNF) to TrkB NGF TrkA induce cell survival neuronal plasticity. After aerobic high-intensity interval training, increase VEGF, angiopoietin 1 2, NO, tPA, HCAR1 cerebral vessels blood flow angiogenesis cerebellum, motor cortex, striatum, hippocampus. In hippocampus, decreases fragmentation, DRP1, FIS1, improving OPA1, MFN1, MFN2, morphology. humans, acute as anti-inflammatory condition IL-6 such IL-1RA IL-10. Moderate-intensity also inhibits inflammatory markers IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, NF-κB. significantly increases plasma BDNF, factor, plasticity, activity, memory, exploratory behavior subjects. Irisin myokine released from skeletal muscle during protects hippocampus by suppressing Aβ accumulation promoting proliferation STAT3 signaling. Therefore, combined strength balance coordination social activities seems provide important benefits for people

Language: Английский

Citations

47
New Insights into Oxidative Stress and Inflammatory Response in Neurodegenerative Diseases DOI Open Access
Eveljn Scarian, Camilla Viola, Francesca Dragoni

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2698 - 2698

Published: Feb. 26, 2024

Oxidative stress (OS) and inflammation are two important well-studied pathological hallmarks of neurodegenerative diseases (NDDs). Due to elevated oxygen consumption, the high presence easily oxidizable polyunsaturated fatty acids weak antioxidant defenses, brain is particularly vulnerable oxidative injury. Uncertainty exists over whether these deficits contribute development NDDs or solely a consequence neuronal degeneration. Furthermore, linked, it known that OS can affect inflammatory response. In this review, we will overview last findings about pathways in principal NDDs. Moreover, focus more depth on amyotrophic lateral sclerosis (ALS) understand how anti-inflammatory antioxidants drugs have been used for treatment still incurable motor neuron (MN) disease. Finally, analyze past actual clinical trials future perspectives study mechanisms.

Language: Английский

Citations

46