Neuron, Год журнала: 2022, Номер 111(1), С. 15 - 29.e8
Опубликована: Ноя. 10, 2022
Язык: Английский
Neuron, Год журнала: 2022, Номер 110(21), С. 3458 - 3483
Опубликована: Ноя. 1, 2022
Язык: Английский
Процитировано
1091
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Сен. 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.
Язык: Английский
Процитировано
480
Immunity, Год журнала: 2021, Номер 54(10), С. 2194 - 2208
Опубликована: Окт. 1, 2021
Язык: Английский
Процитировано
456
Nature, Год журнала: 2023, Номер 615(7953), С. 668 - 677
Опубликована: Март 8, 2023
Язык: Английский
Процитировано
356
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Фев. 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
Язык: Английский
Процитировано
283
Ageing Research Reviews, Год журнала: 2021, Номер 72, С. 101464 - 101464
Опубликована: Сен. 20, 2021
Alzheimer's disease (AD) is a complex neurodegenerative in the elderly and most common cause of human dementia. AD characterized by accumulation abnormal protein aggregates including amyloid plaques (composed beta-amyloid (Aβ) peptides) neurofibrillary tangles (formed hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction patients. Autophagy an evolutionarily conserved lysosome-dependent cellular event eukaryotes. It closely linked to modulation metabolism, through which damaged organelles mis-folded proteins are degraded then recycled maintain homeostasis. Accumulating evidence has shown that impaired autophagy contributes pathogenesis. In present review, we highlight role autophagy, bulk selective regulating metabolic circuits We discuss potential future perspectives autophagy-inducing strategies therapeutics.
Язык: Английский
Процитировано
229
Ageing Research Reviews, Год журнала: 2021, Номер 72, С. 101503 - 101503
Опубликована: Окт. 29, 2021
Язык: Английский
Процитировано
206
Cell, Год журнала: 2022, Номер 185(22), С. 4135 - 4152.e22
Опубликована: Окт. 1, 2022
Recent studies have begun to reveal critical roles for the brain's professional phagocytes, microglia, and their receptors in control of neurotoxic amyloid beta (Aβ) myelin debris accumulation neurodegenerative disease. However, intracellular molecules that orchestrate neuroprotective functions microglia remain poorly understood. In our studies, we find targeted deletion SYK leads exacerbated Aβ deposition, aggravated neuropathology, cognitive defects 5xFAD mouse model Alzheimer's disease (AD). Disruption signaling this AD was further shown impede development disease-associated (DAM), alter AKT/GSK3β-signaling, restrict phagocytosis by microglia. Conversely, receptor-mediated activation limits load. We also found critically regulates microglial DAM acquisition demyelinating Collectively, these results broaden understanding key innate immune instruct beneficial response material.
Язык: Английский
Процитировано
190
Science, Год журнала: 2023, Номер 380(6640)
Опубликована: Апрель 6, 2023
Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.
Язык: Английский
Процитировано
182
Immunity, Год журнала: 2022, Номер 55(12), С. 2236 - 2254
Опубликована: Ноя. 8, 2022
Язык: Английский
Процитировано
176