Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 30, 2023

Abstract Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer’s disease (AD), and its accumulation has been considered as molecular driver pathogenesis progression. Aβ prime target for development AD therapy. However, repeated failures Aβ-targeted clinical trials have cast considerable doubt on amyloid cascade hypothesis whether drug followed correct course. recent successes targeted assuaged those doubts. In this review, we discussed evolution over last 30 years summarized application diagnosis modification. particular, extensively pitfalls, promises important unanswered questions regarding current anti-Aβ therapy, well strategies further study more feasible approaches optimization prevention treatment.

Язык: Английский

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Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

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

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Deregulated mitochondrial microRNAs in Alzheimer's disease: Focus on synapse and mitochondria

Ageing Research Reviews, Год журнала: 2021, Номер 73, С. 101529 - 101529

Опубликована: Ноя. 20, 2021

Язык: Английский

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Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(18), С. 10572 - 10572

Опубликована: Сен. 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

Язык: Английский

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Metabolic Syndrome as a Risk Factor for Alzheimer’s Disease: A Focus on Insulin Resistance

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4354 - 4354

Опубликована: Фев. 22, 2023

Alzheimer's disease (AD) is the main type of dementia and a with profound socioeconomic burden due to lack effective treatment. In addition genetics environmental factors, AD highly associated metabolic syndrome, defined as combination hypertension, hyperlipidemia, obesity 2 diabetes mellitus (T2DM). Among these risk connection between T2DM has been deeply studied. It suggested that mechanism linking both conditions insulin resistance. Insulin an important hormone regulates not only peripheral energy homeostasis but also brain functions, such cognition. desensitization, therefore, could impact normal function increasing developing neurodegenerative disorders in later life. Paradoxically, it demonstrated decreased neuronal signalling can have protective role aging protein-aggregation-associated diseases, case AD. This controversy fed by studies focused on signalling. However, action other cell types, astrocytes, still unexplored. Therefore, worthwhile exploring involvement astrocytic receptor cognition, well onset and/or development

Язык: Английский

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MicroRNAs: pioneering regulators in Alzheimer’s disease pathogenesis, diagnosis, and therapy

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Сен. 10, 2024

Язык: Английский

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Role of JAK/STAT in the Neuroinflammation and its Association with Neurological Disorders

Annals of Neurosciences, Год журнала: 2021, Номер 28(3-4), С. 191 - 200

Опубликована: Июль 1, 2021

Background: Innate immunity is mediated by a variety of cell types, including microglia, macrophages, and neutrophils, serves as the immune system's first line defense. There are numerous pathways involved in innate immunity, interferon (IFN) pathway, TRK mitogen-activated protein kinase (MAPK) Janus kinase/signal transducer activator transcription (JAK/STAT) interleukin (IL) pathways, chemokine (CCR5), GSK signaling, Fas signaling. Summary: JAK/STAT one these important signaling this review focused on pathway only. The overactivation microglia astrocytes influences JAK/STAT's role neuroinflammatory disease initiating orchestrating adaptive mechanisms, ultimately constraining inflammatory immunological responses. critical factors that promotes neuroinflammation neurodegenerative diseases. Key message: Given importance disease, discussed feasibility targeting neuroprotective therapy for diseases near future.

Язык: Английский

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Therapeutic Potential of TNF-α Inhibition for Alzheimer’s Disease Prevention

Journal of Alzheimer s Disease, Год журнала: 2020, Номер 78(2), С. 619 - 626

Опубликована: Сен. 29, 2020

Background: Alzheimer’s disease (AD) is increasingly prevalent and over 99% of drugs developed for AD have failed in clinical trials. A growing body literature suggests that potent inhibitors tumor necrosis factor-α (TNF-α) potential to improve cognitive performance. Objective: In this review, we summarize the evidence regarding TNF-α inhibition prevent function people at risk dementia. Methods: We conducted a review PubMed, screening all articles published before July 7, 2019 related TNF blocking agents curcumin (another inhibitor) context pathology. The keywords search included: AD, dementia, memory, cognition, TNF-α, inhibitors, etanercept, infliximab, adalimumab, golimumab, curcumin. Results: Three large epidemiology studies reported etanercept treated patients had 60 70% lower odds ratio (OR) developing AD. Two small-randomized control trials (RCTs) demonstrated an improvement performance with etanercept. Studies using animal models dementia also similar findings (etanercept, Theracurmin), which appeared cognition. small human RCT Theracurmin, well-absorbed form lowers showed enhanced decreased brain levels amyloid-β plaque tau tangles. Conclusion: targeted therapy biologically plausible approach preservation warrants larger prospective RCTs further investigate benefits populations

Язык: Английский

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Th17 cells and inflammation in neurological disorders: Possible mechanisms of action

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июль 22, 2022

Neurological disorders (NDs) are one of the leading causes global death. A sustained neuroinflammatory response has been reported to be associated with pathogenesis multiple NDs, including Parkinson’s disease (PD), sclerosis (MS), Alzheimer’s (AD), amyotrophic lateral (ALS), and major depressive disorder (MDD). Accumulating evidence shows that recruitment abundant lymphocytes in central nervous system may contribute promoting development progress inflammation neurological disorders. As subset T lymphocytes, CD4 + cells have a critical impact on helper (Th) 17 is most studied Th subpopulations produces cytokines (e.g., IL-17A, IL-23, IL-21, IL-6, IFN-γ), abnormal excessive activation microglia other immune cell types. All these factors involved several However, possible mechanisms Th17 their immunopathology abovementioned not clarified completely. This review will summarize by which encephalitogenic inflammatory related strongly chronic neuroinflammation, thus perpetuating neurodegenerative processes NDs. Finally, potential therapeutic prospects NDs also discussed.

Язык: Английский

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Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings

Cells, Год журнала: 2021, Номер 10(10), С. 2581 - 2581

Опубликована: Сен. 28, 2021

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Most AD patients develop in late life, named onset (LOAD). Currently, most recognized explanation for pathology amyloid cascade hypothesis. It assumed that beta (Aβ) aggregation and deposition are critical pathogenic processes AD, to formation plaques, as well neurofibrillary tangles, neuronal cell death, synaptic degeneration, dementia. In LOAD, causes Aβ accumulation loss not completely clear. Importantly, blood–brain barrier (BBB) disruption seems present an essential role induction neuroinflammation consequent development. addition, we propose systemic inflammation triggered by conditions like metabolic diseases or infections causative factors BBB disruption, coexistent inflammatory and, ultimately, neurodegeneration observed AD. this regard, use anti-inflammatory molecules could be interesting strategy treat, delay even halt progression. Herein, review underlying mechanisms involved pathogenesis revise effects compounds emerging therapeutic drugs against

Язык: Английский

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