Nature Aging, Journal Year: 2023, Volume and Issue: 3(2), P. 202 - 212
Published: Jan. 9, 2023
Language: Английский
Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 31 - 55
Published: Jan. 1, 2022
Language: Английский
Citations
1161
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: Sept. 22, 2023
Abstract Microglia activation is observed in various neurodegenerative diseases. Recent advances single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified specific states correlate pathological hallmarks are associated functions. both exert protective function by phagocytosing clearing protein aggregates play detrimental roles due to excessive uptake of aggregates, which would lead microglial phagocytic ability impairment, neuroinflammation, eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes into a pro-inflammatory phenotype accelerates disease progression. also act as mobile vehicle propagate aggregates. Extracellular vesicles released from autophagy impairment all contribute progression Thus, enhancing phagocytosis, reducing microglial-mediated inhibiting exosome synthesis secretion, promoting conversion considered be promising strategies for the therapy Here we comprehensively review biology diseases, including Alzheimer’s disease, Parkinson’s multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia Lewy bodies Huntington’s disease. We summarize possible microglia-targeted interventions treatments against diseases preclinical clinical evidence cell experiments, animal studies, trials.
Language: Английский
Citations
459
Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(6), P. 2659 - 2673
Published: March 31, 2022
Abstract The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange compounds between the blood and parenchyma. Moreover, BBB prevents unwanted toxins pathogens from entering brain. This barrier, however, breaks down with age further disruption a hallmark many age-related disorders. Several drugs have been explored, thus far, to protect or restore function. With recent connection gut microbiota, microbial-derived metabolites explored their capabilities physiology. review, will focus on components that make up BBB, dissect levels discuss current therapeutics maintain integrity discoveries effects
Language: Английский
Citations
386
Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(37)
Published: Sept. 8, 2021
Significance Impaired neuronal bioenergetics and neuroinflammation are thought to play key roles in the progression of Alzheimer's disease (AD), but their interplay is not clear. AD mouse brains showed lower nicotinamide adenine dinucleotide (NAD + ) levels alterations inflammation. Treatment mice with NR reduced neuroinflammation, attenuated DNA damage, prevented cellular senescence. We present evidence that beneficial effects riboside (NR) are, part, through a cyclic GMP-AMP synthase (cGAS)–stimulator interferon genes (STING)-dependent pathway. damage was increased by NR. Both cGAS–STING NAD pathways potential therapeutic targets for AD.
Language: Английский
Citations
331
Nutrients, Journal Year: 2021, Volume and Issue: 13(11), P. 4080 - 4080
Published: Nov. 15, 2021
Multiple factors combined are currently recognized as contributors to cognitive decline. The main independent risk factor for impairment and dementia is advanced age followed by other determinants such genetic, socioeconomic, environmental factors, including nutrition physical activity. In the next decades, a rise in cases expected due largely aging of world population. There no hitherto effective pharmaceutical therapies treat age-associated dementia, which underscores crucial role prevention. A relationship among diet, activity, lifestyle with function has been intensively studied mounting evidence supporting these development decline chief cause disability globally. Several dietary patterns, foods, nutrients have investigated this regard, some encouraging disappointing results. This review presents current effects components, supplements, sleep social engagement on prevention or delay onset age-related dementia.
Language: Английский
Citations
271
Inflammation, Journal Year: 2022, Volume and Issue: 46(1), P. 1 - 17
Published: Aug. 20, 2022
Language: Английский
Citations
265
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Feb. 16, 2024
Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management
Language: Английский
Citations
255
Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(10), P. 579 - 596
Published: Aug. 26, 2022
Language: Английский
Citations
208
Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)
Published: Sept. 16, 2021
Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD
Language: Английский
Citations
203
Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)
Published: March 21, 2022
Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology site disease pathology. To address these and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus the Melza M. Frank Theodore Barr Foundation collaborated to bring together key opinion leaders experts field for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style focused uncovering mechanistic roots promising new catalyzed by goal finding treatments glaucoma, world's leading cause irreversible blindness interest three hosting foundations. Glaucoma, which causes vision loss through degeneration optic nerve, likely shares early cellular molecular events with other diseases central nervous system. Here we major areas overlap between system: neuroinflammation, bioenergetics metabolism, genetic contributions, neurovascular interactions. We summarize important discussion points emphasis research that are most innovative treatment neurodegeneration yet require further development. The is highlighted provides unique opportunities collaboration will lead efforts preventing ultimately loss.
Language: Английский
Citations
196