Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Язык: Английский

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The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(4), С. 306 - 318

Опубликована: Фев. 17, 2022

Язык: Английский

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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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The China Alzheimer Report 2022

General Psychiatry, Год журнала: 2022, Номер 35(1), С. e100751 - e100751

Опубликована: Фев. 1, 2022

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) related dementias (ADRD). AD's incidence rate, morbidity, mortality steadily increased to make it presently fifth leading cause death among urban rural residents in China magnify resulting financial burdens on individuals, families society. The 'Healthy Action' plan 2019-2030 promotes transition from treatment health maintenance for this expanding with ADRD. This report describes epidemiological trends, evaluates burden disease, outlines current clinical diagnosis status delineates existing available public resources. More specifically, examines impact ADRD, including prevalence, mortality, costs, usage care, overall effect caregivers In addition, special presents technical guidance supports prevention AD, provides expertise guide relevant governmental healthcare policy suggests an information platform international exchange cooperation.

Язык: Английский

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ApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias

Neuron, Год журнала: 2022, Номер 110(8), С. 1304 - 1317

Опубликована: Март 16, 2022

Язык: Английский

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Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer’s Disease: A Focus on Aducanumab and Lecanemab

Frontiers in Aging Neuroscience, Год журнала: 2022, Номер 14

Опубликована: Апрель 12, 2022

Alzheimer's disease (AD) is the most prevalent form of age-related dementia in world, and its main pathological features consist amyloid-β (Aβ) plaque deposits neurofibrillary tangles formed by hyperphosphorylated tau protein. So far, only a few AD treatments approved have been applied clinic, but effects these drugs are limited for partial symptomatic relief to patients with unable alter progression. Later, all efforts targeting pathogenic factors were unsuccessful over past decades, which suggested that pathogenesis complex. Recently, disease-modifying therapies (DMTs) can change underlying pathophysiology AD, anti-Aβ monoclonal antibodies (mabs) (e.g., aducanumab, bapineuzumab, gantenerumab, solanezumab, lecanemab) developed successively conducted clinical trials based on theory systemic failure cell-mediated Aβ clearance contributes occurrence In review, we summarized recent studies therapeutic trial results mabs AD. Specifically, focused discussion impact aducanumab lecanemab pathology profiles. The review provides possible evidence applying immunotherapy analyzes lessons learned from order further study adverse

Язык: Английский

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Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease

Ageing Research Reviews, Год журнала: 2021, Номер 68, С. 101339 - 101339

Опубликована: Апрель 5, 2021

Язык: Английский

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Aducanumab: evidence from clinical trial data and controversies

Drugs in Context, Год журнала: 2021, Номер 10, С. 1 - 9

Опубликована: Сен. 30, 2021

Alzheimer's disease (AD) is the most common cause for dementia worldwide. Until recently, all approved treatments AD were symptomatic and not modifying. On 7 June 2021, US FDA aducanumab, a human IgG1 anti-Aβ monoclonal antibody selective Aβ aggregates, as first disease-modifying treatment AD. Aducanumab in United States of mild cognitive impairment or mild-dementia stage In this Editorial, we review trial data aducanumab controversies that its approval has generated.

Язык: Английский

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Brain borders at the central stage of neuroimmunology

Nature, Год журнала: 2022, Номер 612(7940), С. 417 - 429

Опубликована: Дек. 14, 2022

Язык: Английский

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Role of Aducanumab in the Treatment of Alzheimer’s Disease: Challenges and Opportunities

Clinical Interventions in Aging, Год журнала: 2022, Номер Volume 17, С. 797 - 810

Опубликована: Май 1, 2022

Abstract: Aducanumab is a monoclonal antibody selective for amyloid β (Aβ) aggregates. In June 2021, aducanumab became the first drug underlying pathophysiology of Alzheimer's disease (AD) approved by US Food and Drug Administration (FDA), under accelerated approval pathway. The decision was based on ability to remove Aβ plaques, without any evidence that clearance correlated with less cognitive or functional decline. This has generated considerable debate in scientific community, especially because results from two Phase 3 trials, EMERGE ENGAGE, were divergent and, even after post hoc analysis, data insufficient prove efficacy. Moreover, some researchers think this will be an obstacle progress also demonstrated concerns about cost its safety profile. European Medicines Agency's rejection December 2021 just brought more controversy over FDA's decision. Now, Biogen designing required confirmatory study, named ENVISION, which should complete 2026. Despite controversy, showed affect downstream tau pathology, could open doors combination therapy approach AD (anti-tau anti-amyloid drug). review summarizes clinical development until regulatory agencies' decisions, available trials AD. Keywords: anti-Aβ antibody, ARIA, Agency, Administration, protein

Язык: Английский

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