Current topics in membranes, Год журнала: 2023, Номер unknown, С. 199 - 231
Опубликована: Янв. 1, 2023
Язык: Английский
Drugs, Год журнала: 2023, Номер 83(15), С. 1387 - 1408
Опубликована: Сен. 20, 2023
Novel agents addressing non-amyloid, non-tau targets in Alzheimer's Disease (AD) comprise 70% of the AD drug development pipeline currently clinical trials. Most target processes identified Common Research Ontology (CADRO) are represented by novel Inflammation and synaptic plasticity/neuroprotection CADRO categories with largest number candidate therapies. Within these categories, there few overlapping among test agents. Additional being evaluated include apolipoprotein E $$\varepsilon$$ 4 (APOE4) effects, lipids lipoprotein receptors, neurogenesis, oxidative stress, bioenergetics metabolism, vascular factors, cell death, growth factors hormones, circadian rhythm, epigenetic regulators. We highlight current drugs tested within their mechanisms. Trials will be informative regarding which can modulated to produce a slowing decline. Possible therapeutic combinations may suggested trial outcomes. Biomarkers evolving concert new agents, biomarker outcomes offer means supporting disease modification putative treatment. Identification corresponding therapeutics an important advancing treatments for AD.
Язык: Английский
Процитировано
69
EBioMedicine, Год журнала: 2025, Номер 113, С. 105612 - 105612
Опубликована: Фев. 25, 2025
Язык: Английский
Процитировано
3
Aging and Disease, Год журнала: 2023, Номер unknown, С. 0 - 0
Опубликована: Янв. 1, 2023
Alzheimer’s disease, one of the most common forms dementia, is characterized by a slow progression cognitive impairment and neuronal loss. Currently, approved treatments for AD are hindered various side effects limited efficacy. Despite considerable research, practical have not been developed. Increasing evidence shows that glial cells, especially microglia astrocytes, essential in initiation AD. During progression, activated resident increases ability resting astrocytes to transform into reactive promoting neurodegeneration. Extensive clinical molecular studies show involvement astrocyte-mediated neuroinflammation pathology, indicating may be potential therapeutic targets This review will summarize significant recent advances pathogenesis three parts. First, we typical pathological changes discuss terms function phenotypic changes. Second, describe astrocytes’ physiological role These roles include inflammatory response, “eat me” “don’t eat signals, Aβ seeding, propagation, clearance, synapse loss, synaptic pruning, remyelination, demyelination. Last, pharmacological non-pharmacological therapies targeting We conclude development Therefore, understanding new critical future trials. Moreover, pharmacological, with specific investigating damage repair, promising research direction regarding treatment prevention.
Язык: Английский
Процитировано
36
Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15
Опубликована: Ноя. 23, 2023
Cellular senescence is a biological aging hallmark that plays key role in the development of neurodegenerative diseases. Clinical trials are currently underway to evaluate effectiveness senotherapies for these However, impact on brain and cognitive decline absence neurodegeneration remains uncertain. Moreover, patient populations like cancer survivors, traumatic injury obese individuals, obstructive sleep apnea patients, chronic kidney disease patients can suffer age-related changes prematurely, suggesting they may accelerated brain. Understanding neurocognitive deficits linked conditions crucial, especially considering rapidly evolving field senotherapeutics. Such treatments could help alleviate early significantly reducing morbidity healthcare costs. This review provides translational perspective how cellular decline. We also discuss important caveats surrounding mainstream senolytics senomorphics, present emerging evidence hyperbaric oxygen therapy immune-directed therapies as viable modalities senescent cell burden.
Язык: Английский
Процитировано
28
Brain Communications, Год журнала: 2024, Номер 6(2)
Опубликована: Янв. 1, 2024
Abstract Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds infection) alter cellular physiologic processes within the neurovascular unit contribute cognitive dysfunction. COVID-19 has posed significant complications during acute convalescent stages in multiple organ systems, including brain. Cognitive impairment is prevalent complication patients, irrespective of severity SARS-CoV-2 infection. Moreover, overwhelming evidence from vitro, preclinical clinical studies reported SARS-CoV-2-induced pathologies components are associated with impairment. Neurovascular disruption alters coupling response, critical mechanism regulates cerebromicrovascular blood flow meet energetic demands locally active neurons. Normal processing achieved through response involves coordinated action cells (i.e. neurons glia) cell types endothelia, smooth muscle pericytes). However, current work on COVID-19-induced yet investigate as causal factor. Hence, this review, we aim describe SARS-CoV-2's effects how they can impact decline disease. Additionally, explore potential therapeutic interventions mitigate Given great both individuals public health, necessity effort fundamental scientific research application becomes imperative. This integrated endeavour crucial mitigating deficits induced by its subsequent burden especially vulnerable population.
Язык: Английский
Процитировано
13
Translational research, Год журнала: 2025, Номер 278, С. 36 - 47
Опубликована: Фев. 20, 2025
Язык: Английский
Процитировано
1
Antioxidants, Год журнала: 2023, Номер 12(8), С. 1646 - 1646
Опубликована: Авг. 21, 2023
Fisetin has been shown to be beneficial for brain injury and age-related disease via different mechanisms. The purpose of this study was determine the presence senescent cells effects fisetin on cellular senescence in other vital organs old sheep, a more translational model. Female sheep 6–7 years (N = 6) were treated with 100 mg/kg or vehicle alone two consecutive days week 8 weeks. All harvested at time sacrifice. Histology, immunofluorescence staining, RT-Q-PCR performed regions tissues organs. Our results indicated that treatment current regimen did not affect general morphology brain. both cerebral cortex cerebellum non-Cornu Ammonis (CA) area hippocampus detected by senescent-associated β-galactosidase (SA-β-Gal) staining GL13 (lipofuscin) staining. mainly neurons gray white matter either cortex, cerebellum, non-CA hippocampus. Very few CA1-4 hippocampus, as revealed GLB1 colocalization NEUN. significantly decreased number SA-β-Gal+ GL13+ showed decreasing trend cerebellum. Furthermore, P16+ GLB1+ neuronal nuclear protein (NEUN)+ neurons, glial fibrillary acidic (GFAP)+ astrocytes, ionized calcium binding adaptor molecule 1 (IBA1)+ microglia cortex. cells, NEUN+ plasma S100B. At mRNA level, downregulated liver, lung, heart, spleen tissues, P21 expression liver lung. TREM2 lung downregulation spleen, heart. A significant decrease NRLP3 observed after treatment. Finally, SOD1 while upregulating CAT spleen. In conclusion, we found widely present sheep. addition, gene expressions inflammasomes organs, such liver. represents promising therapeutic strategy diseases.
Язык: Английский
Процитировано
15
Pharmaceuticals, Год журнала: 2024, Номер 17(1), С. 70 - 70
Опубликована: Янв. 4, 2024
Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and polyphenol quercetin is used clinical trials as a senolytic, first results point relief physical dysfunction patients idiopathic pulmonary fibrosis. In this work, we tested new combinations drugs polyphenols, looking for senolytic activity using fibroblasts (MRC-5 cell line) induced senescence. We researched drugs, such azithromycin, rapamycin, metformin, FK-506, aspirin, combined nine natural namely caffeic acid, chlorogenic ellagic ferulic gallic epicatechin, hesperidin, quercetin, resveratrol. found effective acid Both increased apoptosis, reduced BCL-2 expression, caspase MRC-5 cells. Ellagic was more potent than resveratrol counteracted inflammatory cytokine release during senolysis vitro. conclusion, present vitro potential like that observed maybe they could future alternatives senotherapeutic field.
Язык: Английский
Процитировано
6
Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)
Опубликована: Ноя. 1, 2024
The role of senescence in disease contexts is complex, however there considerable evidence that depletion senescent cells improves outcomes a variety particularly related to aging, cognition, and neurodegeneration. Much research has shown previously inflammation can promote cellular senescence. Microglia are central nervous system innate immune cell undergo with aging during contribution microglia multiple sclerosis, an inflammatory neurodegenerative disease, not clear, but strongly implicated chronic active lesion pathology, tissue injury, progression. Drugs could specifically eliminate dysregulated sclerosis therefore great interest the field.
Язык: Английский
Процитировано
6
Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102400 - 102400
Опубликована: Июнь 28, 2024
Язык: Английский
Процитировано
4