A selective p38α/β MAPK inhibitor alleviates neuropathology and cognitive impairment, and modulates microglia function in 5XFAD mouse DOI Creative Commons
Min Sung Gee,

Seung Hwan Son,

Seung Ho Jeon

и другие.

Alzheimer s Research & Therapy, Год журнала: 2020, Номер 12(1)

Опубликована: Апрель 21, 2020

Abstract Background Chronic neuroinflammation, aggressive amyloid beta (Aβ) deposition, neuronal cell loss, and cognitive impairment are pathological presentations of Alzheimer’s disease (AD). Therefore, resolution neuroinflammation inhibition Aβ-driven pathology have been suggested to be important strategies for AD therapy. Previous efforts prevent progression identified p38 mitogen-activated protein kinases (MAPKs) as a promising target Recent studies showed pharmacological p38α MAPK improved memory in mouse models. Methods In this study, we used an model, 5XFAD, explore the therapeutic potential NJK14047 which is novel, selective p38α/β inhibitor. The mice were injected with 2.5 mg/kg or vehicle every other day 3 months. Morris water maze task histological imaging analysis performed. Protein mRNA expression levels measured using immunoblotting qRT-PCR, respectively. vitro conducted measure cytotoxicity microglia- astrocyte-conditioned medium on primary neurons MTT assay TUNEL assay. Results treatment downregulated phospho-p38 levels, decreased amount Aβ deposits, reduced spatial learning loss 9-month-old 5XFAD mice. While pro-inflammatory conditions decreased, alternatively activated microglial markers phagocytic receptors was increased. Furthermore, number degenerating labeled Fluoro-Jade B brains neuroprotective effect further confirmed by studies. Conclusion Taken together, inhibitor successfully effects Based our data, strategy therapy, suggesting one candidates therapeutics targeting MAPKs.

Язык: Английский

RNA 2′-O-Methylation (Nm) Modification in Human Diseases DOI Open Access

Dilyana G. Dimitrova,

Laure Teysset, Clément Carré

и другие.

Genes, Год журнала: 2019, Номер 10(2), С. 117 - 117

Опубликована: Фев. 5, 2019

Nm (2′-O-methylation) is one of the most common modifications in RNA world. It has potential to influence molecules multiple ways, such as structure, stability, and interactions, play a role various cellular processes from epigenetic gene regulation, through translation self versus non-self recognition. Yet, building scientific knowledge on matter been hampered for long time by challenges detecting mapping this modification. Today, with latest advancements area, more sites are discovered RNAs (tRNA, rRNA, mRNA, small non-coding RNA) linked normal or pathological conditions. This review aims synthesize Nm-associated human diseases known date tackle indirect links some other biological defects.

Язык: Английский

Процитировано

164

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

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6518 - 6518

Опубликована: Март 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.

Язык: Английский

Процитировано

123

Role of natural products for the treatment of Alzheimer's disease DOI

Tayebeh Noori,

Ahmad Reza Dehpour, Antoni Sureda

и другие.

European Journal of Pharmacology, Год журнала: 2021, Номер 898, С. 173974 - 173974

Опубликована: Фев. 27, 2021

Язык: Английский

Процитировано

121

CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases DOI

Meena S. Subbarayan,

Aurélie Joly‐Amado,

Paula C. Bickford

и другие.

Pharmacology & Therapeutics, Год журнала: 2021, Номер 231, С. 107989 - 107989

Опубликована: Сен. 4, 2021

Язык: Английский

Процитировано

115

Multimorbidity burden and dementia risk in older adults: The role of inflammation and genetics DOI Creative Commons
Giulia Grande, Alessandra Marengoni, Davide Liborio Vetrano

и другие.

Alzheimer s & Dementia, Год журнала: 2021, Номер 17(5), С. 768 - 776

Опубликована: Янв. 6, 2021

Abstract Introduction We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation apolipoprotein E ( APOE ) genotype. Methods A total 2,478 dementia‐free participants two or more chronic diseases (ie, multimorbidity) part Swedish National study on Aging Care Kungsholmen (SNAC‐K) were grouped according to their multimorbidity followed detect clinical dementia. The potential modifier effect C‐reactive protein (CRP) genotype was tested through stratified analyses. Results People neuropsychiatric , cardiovascular sensory impairment/cancer had increased hazards for compared unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13‐2.42; 1.61, CI 1.17‐2.29; 1.32, 1.10‐1.71, respectively). Despite lack statistically significant interaction, high CRP within these patterns, being ε4 carriers heightened multimorbidity. Discussion Individuals neuropsychiatric, cardiovascular, are at ε4, may further increase risk. Identifying such high‐risk groups might allow tailored interventions prevention.

Язык: Английский

Процитировано

114

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

Mohammad Khushtar

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(2), С. 616 - 616

Опубликована: Янв. 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.

Язык: Английский

Процитировано

95

Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases DOI Creative Commons
Rachel J. Boyd,

Dimitri Avramopoulos,

Lauren L. Jantzie

и другие.

Journal of Neuroinflammation, Год журнала: 2022, Номер 19(1)

Опубликована: Сен. 8, 2022

Multifactorial diseases are characterized by inter-individual variation in etiology, age of onset, and penetrance. These tend to be relatively common arise from the combined action genetic environmental factors; however, parsing convoluted mechanisms underlying these gene-by-environment interactions presents a significant challenge their study management. For neurodegenerative disorders, resolving this is imperative, given enormous health societal burdens they impose. The which effects may act concert destabilize homeostasis elevate risk has become major research focus disease. Emphasis further being placed on determining extent unifying biological principle account for progressively diminishing capacity system buffer disease phenotypes, as increases. Data emerging studies common, providing insights pragmatically connect that previously seemed disparate. In review, we discuss evidence positing inflammation homeostatic destabilization affecting risk, progression diseases. Specifically, how associated with Alzheimer Parkinson contribute pro-inflammatory responses, such predisposition exacerbated insults, theme leveraged ongoing search effective therapeutic interventions.

Язык: Английский

Процитировано

80

Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies DOI Open Access
Amer E. Alkhalifa,

Nour F. Al-Ghraiybah,

Julia Odum

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16288 - 16288

Опубликована: Ноя. 14, 2023

The blood-brain barrier (BBB) is a unique and selective feature of the central nervous system's vasculature. BBB dysfunction has been observed as an early sign Alzheimer's Disease (AD) before onset dementia or neurodegeneration. intricate relationship between pathogenesis AD, especially in context neurovascular coupling overlap pathophysiology neurodegenerative cerebrovascular diseases, underscores urgency to understand BBB's role more deeply. Preserving restoring function emerges potentially promising strategy for mitigating progression severity AD. Molecular genetic changes, such isoform ε4 apolipoprotein E (ApoEε4), significant risk factor promoter dysfunction, have shown mediate disruption. Additionally, receptors transporters like low-density lipoprotein receptor-related protein 1 (LRP1), P-glycoprotein (P-gp), receptor advanced glycation end products (RAGEs) implicated AD's pathogenesis. In this comprehensive review, we endeavor shed light on pathogenic therapeutic connections AD BBB. We also delve into latest developments pioneering strategies targeting interventions, addressing its potential carrier. By providing integrative perspective, anticipate paving way future research treatments focused exploiting therapy.

Язык: Английский

Процитировано

70

Innovative Therapy for Alzheimer’s Disease-With Focus on Biodelivery of NGF DOI Creative Commons
Sumonto Mitra, Homira Behbahani, Maria Eriksdotter

и другие.

Frontiers in Neuroscience, Год журнала: 2019, Номер 13

Опубликована: Фев. 4, 2019

Alzheimer's disease (AD) is a devastating neurological condition associated with abnormal protein modification, inflammation and memory impairment. Aggregated amyloid beta (Aβ) phosphorylated tau proteins are medical diagnostic features but detected only after the has progressed to advanced stages. The loss of in AD been central cholinergic dysfunction basal forebrain, where circuitry projects cerebral cortex hippocampus. Current medications target acetylcholine metabolism stabilize decline. Various reports link progression declining activity forebrain neurons. neurotrophin, nerve growth factor (NGF), enhances survival effects neurons, which retrogradely transported from hippocampus forebrain. Recent studies have shown that NGF plays role aging as well age-related diseases such AD, since can interact pre-existing abnormalities trophic signalling trigger cognitive decline observed AD. Further, gradual dysregulation neurotrophic factors brain derived (BDNF) during development thus intensifying further research targeting these modifying therapies against Today, there no cure available for symptomatic treatment like cholinesterase inhibitors (ChEIs) memantine transient moderate. Although many carried out, yet breakthrough new highly needed. Therefore need review advancements its potential therapeutic implications In this review, we will put emphasis on focus encapsulated biodelivery (ECB) therapy method summary, hope describe experimental clinical data, demonstrating important roles treatment, an efficient

Язык: Английский

Процитировано

141

Cathepsin B in neurodegeneration of Alzheimer's disease, traumatic brain injury, and related brain disorders DOI
Vivian Hook, Michael C. Yoon,

Charles Mosier

и другие.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Год журнала: 2020, Номер 1868(8), С. 140428 - 140428

Опубликована: Апрель 17, 2020

Язык: Английский

Процитировано

135