New insight on microglia activation in neurodegenerative diseases and therapeutics DOI Creative Commons

Yucong Xu,

Wei Gao, Yingnan Sun

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Dec. 22, 2023

Microglia are immune cells within the central nervous system (CNS) closely linked to brain health and neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease. In response changes in surrounding environment, microglia activate change their state function. Several factors, example for circadian rhythm disruption development of diseases, influence activation. this review, we explore microglia’s function associated neural mechanisms. We elucidate that rhythms essential factors influencing activation Circadian affects and, consequently, diseases. addition, found abnormal is a common feature an factor development. Here highlight importance Targeting treatment promising direction. introduce progress methods targeting summarize drugs developed with targets, hoping provide new ideas treating

Language: Английский

Circadian rhythms and disorders of the timing of sleep DOI
Nicholas Meyer, Allison G. Harvey, Steven W. Lockley

et al.

The Lancet, Journal Year: 2022, Volume and Issue: 400(10357), P. 1061 - 1078

Published: Sept. 1, 2022

Language: Английский

Citations

172
Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease DOI Creative Commons
Minghui Wang, Hu Zhang, Jiling Liang

et al.

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: March 19, 2023

Abstract Alzheimer’s disease (AD) is a chronic neurodegenerative disease, with the characteristics of neurofibrillary tangle (NFT) and senile plaque (SP) formation. Although great progresses have been made in clinical trials based on relevant hypotheses, these studies are also accompanied by emergence toxic side effects, it an urgent task to explore underlying mechanisms for benefits prevent treat AD. Herein, animal experiments few trials, neuroinflammation AD characterized long-term activation pro-inflammatory microglia NOD-, LRR- pyrin domain-containing protein 3 (NLRP3) inflammasomes. Damaged signals from periphery within brain continuously activate microglia, thus resulting constant source inflammatory responses. The response exacerbates endoplasmic reticulum oxidative stress which triggers microglia-dependent immune responses, ultimately leading occurrence deterioration In this review, we systematically summarized sorted out that exercise ameliorates directly indirectly regulating central nervous system promoting hippocampal neurogenesis provide new direction exploring activity

Language: Английский

Citations

83
Circadian disruption and sleep disorders in neurodegeneration DOI Creative Commons

Yun Shen,

Qian‐Kun Lv,

Wei-Ye Xie

et al.

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Feb. 13, 2023

Abstract Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions diseases. Circadian disruption disorders aggravate neurodegeneration in turn disrupt sleep. Importantly, various increase the risk Thus, harnessing biology findings from preclinical translational research is importance for reducing improving symptoms quality life individuals with via approaches that normalize context precision medicine. In this review, we discuss implications by summarizing both human animal studies, focusing on links prevalent forms neurodegeneration. These provide valuable insights into pathogenesis suggest promising role circadian-based interventions.

Language: Английский

Citations

65
Metabolic diseases and healthy aging: identifying environmental and behavioral risk factors and promoting public health DOI Creative Commons
Kexin Zhang,

Yujie Ma,

Youhong Luo

et al.

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 13, 2023

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue cellular functions, along with significant increase risk of various aging-related diseases, including metabolic diseases. While advances modern medicine have significantly promoted human health extended lifespan, diseases such obesity type 2 diabetes among older adults pose major challenge to global public societies age. Therefore, understanding complex interaction between factors crucial for promoting well-being healthy aging. This review article explores environmental behavioral associated their impact on The environment, an obesogenic environment exposure toxins, strongly correlated rising prevalence its comorbidities. Behavioral factors, diet, physical activity, smoking, alcohol consumption, sleep patterns, influence throughout Public interventions targeting modifiable can effectively promote healthier lifestyles prevent Collaboration government agencies, healthcare providers community organizations essential implementing these creating supportive environments foster

Language: Английский

Citations

56
Non-Invasive Drug Delivery across the Blood–Brain Barrier: A Prospective Analysis DOI Creative Commons
Sarfaraz K. Niazi

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(11), P. 2599 - 2599

Published: Nov. 7, 2023

Non-invasive drug delivery across the blood–brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is tightly packed layer of endothelial cells that shields brain from harmful substances blood, allowing necessary nutrients to pass through. It highly selective barrier, which poses challenge delivering therapeutic agents into brain. Several non-invasive procedures and devices have been developed or are currently being investigated enhance BBB. This paper presents review prospective analysis art science address pharmacology, technology, systems, regulatory approval, ethical concerns, future possibilities.

Language: Английский

Citations

43
Biologically informed deep learning for explainable epigenetic clocks DOI Creative Commons

Aurél Prósz,

Orsolya Pipek, Judit Börcsök

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 15, 2024

Abstract Ageing is often characterised by progressive accumulation of damage, and it one the most important risk factors for chronic disease development. Epigenetic mechanisms including DNA methylation could functionally contribute to organismal aging, however key functions biological processes may govern ageing are still not understood. Although age predictors called epigenetic clocks can accurately estimate an individual based on cellular methylation, their models have limited ability explain prediction algorithm behind underlying controlling ageing. Here we present XAI-AGE, a biologically informed, explainable deep neural network model accurate across multiple tissue types. We show that XAI-AGE outperforms first-generation achieves similar results learning-based models, while opening up possibility infer meaningful insights activity pathways other abstract directly from model.

Language: Английский

Citations

17
Sleep and circadian rhythms in Parkinson’s disease and preclinical models DOI Creative Commons
Jeremy Hunt, Elizabeth J. Coulson, Rajendram V. Rajnarayanan

et al.

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: Jan. 9, 2022

The use of animals as models human physiology is, and has been for many years, an indispensable tool understanding the mechanisms disease. In Parkinson's disease, various mouse form cornerstone these investigations. Early were developed to reflect traditional histological features motor symptoms However, it is important that accurately encompass facets disease allow comprehensive mechanistic translational significance. Circadian rhythm sleep issues are tightly correlated often arise prior presentation typical deficits. It essential used understand dysfunctions in circadian rhythms sleep, both facilitate investigations into interplay between assist development rhythm-facing therapeutic treatments. This review describes extent which genetically- neurotoxically-induced murine abnormalities observed clinic.

Language: Английский

Citations

63
Fasting: From Physiology to Pathology DOI Creative Commons
Dongmei Tang,

Qiuyan Tang,

Wei Huang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(9)

Published: Feb. 3, 2023

Overnutrition is a risk factor for various human diseases, including neurodegenerative metabolic disorders, and cancers. Therefore, targeting overnutrition represents simple but attractive strategy the treatment of these increasing public health threats. Fasting as dietary intervention combating has been extensively studied. practiced millennia, only recently have its roles in molecular clock, gut microbiome, tissue homeostasis function emerged. can slow aging most species protect against These centuried unfading adventures explorations suggest that fasting potential to delay help prevent treat diseases while minimizing side effects caused by chronic interventions. In this review, recent animal studies concerning role underlying mechanism physiology pathology are summarized, therapeutic highlighted, combination pharmacological discussed new regimen diseases.

Language: Английский

Citations

39
Circadian Rhythms and Astrocytes: The Good, the Bad, and the Ugly DOI Creative Commons
Michael H. Hastings, Marco Brancaccio, Maria F. Gonzalez-Aponte

et al.

Annual Review of Neuroscience, Journal Year: 2023, Volume and Issue: 46(1), P. 123 - 143

Published: Feb. 28, 2023

This review explores the interface between circadian timekeeping and regulation of brain function by astrocytes. Although astrocytes regulate neuronal activity across many time domains, their cell-autonomous clocks exert a particular role in controlling longer-term oscillations function: maintenance sleep states ordering wakefulness. is most evident central pacemaker, suprachiasmatic nucleus, where molecular clock suffices to drive daily cycles behavior. In Alzheimer's disease, impairments accompany cognitive decline. mouse models disturbances accelerate astroglial activation other pathologies, suggesting that functions protect homeostasis. cancer, treatment morning has been associated with prolonged survival, gliomas have rhythms gene expression drug sensitivity. Thus, fast becoming critical elucidating reciprocal astrocytic-neuronal interactions health disease.

Language: Английский

Citations

33
The Mammalian Circadian Time-Keeping System DOI Creative Commons
Andrew P. Patton, Michael H. Hastings

Journal of Huntington s Disease, Journal Year: 2023, Volume and Issue: 12(2), P. 91 - 104

Published: April 25, 2023

Our physiology and behavior follow precise daily programs that adapt us to the alternating opportunities challenges of day night. Under experimental isolation, these rhythms persist with a period approximately one (circadian), demonstrating their control by an internal autonomous clock. Circadian time is created at cellular level transcriptional/translational feedback loop (TTFL) in which protein products Period Cryptochrome genes inhibit own transcription. Because accumulation slow delayed, system oscillates spontaneously ∼24 hours. This cell-autonomous TTFL controls cycles gene expression all major tissues underpin our metabolic programs. In turn, innumerable clocks are coordinated central pacemaker, suprachiasmatic nucleus (SCN) hypothalamus. When isolated slice culture, SCN its dependent neural activity indefinitely, operating as "a clock dish". vivo, synchronized solar direct innervation from specialized retinal photoreceptors. circadian cycle action potential firing signals SCN-generated hypothalamic brain stem targets, co-ordinate downstream autonomic, endocrine, behavioral (feeding) cues synchronize sustain distributed network. therefore pervades every biological organization, molecules society. Understanding mechanisms offers important mitigate consequences disruption, so prevalent modern societies, arise shiftwork, aging, neurodegenerative diseases, not least Huntington's disease.

Language: Английский

Citations

33