Metabolic response of microglia to amyloid deposition during Alzheimer’s disease progression in a mouse model DOI Creative Commons
Kaitlyn M. Marino, Jayne M. Squirrell, Jenu V. Chacko

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 12, 2023

Summary Alzheimer’s disease (AD) drives metabolic changes in the central nervous system (CNS). In AD microglia are activated and proliferate response to amyloid β plaques. To further characterize associated with plaque deposition situ , we examined cortical tissue from 2, 4, 8-month-old wild type 5XFAD mice, a mouse model of deposition. mice exhibited progressive microgliosis as well microglial morphology neuronal dystrophy. Multiphoton-based fluorescent lifetime imaging microscopy (FLIM) measurements showed that older had an increased amount free NAD(P)H, indicative shift towards glycolysis. Interestingly also found abundant previously undescribed third fluorescence component suggests alternate NAD(P)H binding partner pathology. This work demonstrates FLIM combination other quantitative methods, is promising label-free tool for understanding mechanisms

Language: Английский

Thirty years of NRF2: advances and therapeutic challenges DOI
Donna D. Zhang

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

11
Wearables in Chronomedicine and Interpretation of Circadian Health DOI Creative Commons
Denis Gubin,

Dietmar Weinert,

Oliver Stefani

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(3), P. 327 - 327

Published: Jan. 30, 2025

Wearable devices have gained increasing attention for use in multifunctional applications related to health monitoring, particularly research of the circadian rhythms cognitive functions and metabolic processes. In this comprehensive review, we encompass how wearables can be used study disease. We highlight importance these as markers well-being potential predictors outcomes. focus on wearable technologies sleep research, medicine, chronomedicine beyond domain emphasize actigraphy a validated tool monitoring sleep, activity, light exposure. discuss various mathematical methods currently analyze actigraphic data, such parametric non-parametric approaches, linear, non-linear, neural network-based applied quantify non-circadian variability. also introduce novel actigraphy-derived markers, which personalized proxies status, assisting discriminating between disease, offering insights into neurobehavioral status. lifestyle factors physical activity exposure modulate brain health. establishing reference standards measures further refine data interpretation improve clinical The review calls existing tools methods, deepen our understanding health, develop healthcare strategies.

Language: Английский

Citations

3
Structure characterization of polysaccharides from Cistanche deserticola and their neuroprotective effects against oxidative stress in slow transit constipation mice DOI
Hongyu Jiang,

Rui-an Ma,

Fulong Ji

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 260, P. 129527 - 129527

Published: Jan. 19, 2024

Language: Английский

Citations

16
Detection of NADH and NADPH levels in vivo identifies shift of glucose metabolism in cancer to energy production DOI
Elena Potapova, Evgeny Zherebtsov, Valery Shupletsov

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(12), P. 2674 - 2682

Published: Feb. 5, 2024

Profound changes in the metabolism of cancer cells have been known for almost 100 years, and many aspects these continued to be actively studied discussed. Differences results various studies can explained by diversity tumours, which differing processes energy metabolism, limitations methods used. Here, using fluorescence lifetime needle optical biopsy a hepatocellular carcinoma (HCC) mouse model patients with HCC, we measured reduced nicotinamide adenine dinucleotide (NADH) phosphate (NADPH) control liver, HCC tumours their adjacent regions. We found that NADH level (mostly responsible metabolism) is increased but also regions same liver. NADPH significantly decreased model. However, ex vivo tumour slices reactive oxygen species production glutathione (both dependent on NADPH) were suppressed. Thus, glucose-dependent changed more pronounced shift (NADH), rather than synthesis redox balance.

Language: Английский

Citations

9
Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation DOI Creative Commons

Mona Breßer,

Kevin D. Siemens, Linda Schneider

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: 17(2), P. 301 - 335

Published: Jan. 6, 2025

Abstract Current studies pictured the enteric nervous system and macrophages as modulators of neuroimmune processes in inflamed gut. Expanding this view, we investigated impact neuron–macrophage interactions on postoperative trauma subsequent motility disturbances, i.e., ileus. In early postsurgical phase, detected strong neuronal activation, followed by transcriptional translational signatures indicating death synaptic damage. Simultaneously, our study revealed neurodegenerative profiles macrophage-specific transcriptomes after trauma. Validating role resident monocyte-derived macrophages, depleted CSF-1R-antibodies used CCR2 −/− mice, known for reduced monocyte infiltration, POI studies. Only CSF-1R-antibody-treated animals showed decreased lessened decay, emphasizing significance macrophages. human gut samples taken late during abdominal surgery, substantiated mouse model data found reactive apoptotic neurons dysregulation genes, a species’ overarching mechanism. Our demonstrates that surgical activates induces neurodegeneration, mediated introducing neuroprotection an option faster recovery surgery.

Language: Английский

Citations

1
Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome DOI
Jiawei Zhang, Weiqiang Lv, Guanfei Zhang

et al.

Antioxidants and Redox Signaling, Journal Year: 2024, Volume and Issue: 41(10-12), P. 744 - 768

Published: Jan. 6, 2024

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis find more effective targets modalities for intervention.

Language: Английский

Citations

6
RAGE induces physiological activation of NADPH oxidase in neurons and astrocytes and neuroprotection DOI
Evgeniya Seryogina, A. V. Kamynina,

Dmitry O. Koroev

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(9), P. 1944 - 1957

Published: Feb. 9, 2024

The transmembrane receptor for advanced glycation end products (RAGE) is a signaling many damage‐ and pathogen‐associated molecules. Activation of RAGE associated with inflammation an increase in reactive oxygen species (ROS) production. Although several sources ROS have been previously suggested, how induces production still unclear, considering the multiple targets Here, using acute brain slices primary co‐culture cortical neurons astrocytes, we investigated effects range synthetic peptides corresponding to fragments V‐domain on redox signaling. We found that fragment (60–76) activation astrocytes from slices. This effect occurred through could be blocked by inhibitor. stimulates NADPH oxidase (NOX). RAGE‐induced NOX produced only minor decreases glutathione levels increased rate lipid peroxidation, although it also reduced basal β‐amyloid induced cell death astrocytes. Thus, specific NOX, which can part protective mechanism.

Language: Английский

Citations

6
Nrf2 as a regulator of energy metabolism and mitochondrial function DOI Creative Commons

Alina Luchkova,

Ana Mata, Susana Cadenas

et al.

FEBS Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Nuclear factor erythroid‐2‐related 2 (Nrf2) is essential for the control of cellular redox homeostasis. When activated, Nrf2 elicits cytoprotective effects through expression several genes encoding antioxidant and detoxifying enzymes. can also improve defense via pentose phosphate pathway by increasing NADPH availability to regenerate glutathione. Microarray genome‐wide localization analyses have identified many target beyond those linked its redox‐regulatory capacity. regulates intermediary metabolic pathways involved in cancer cell reprogramming, contributing malignant phenotypes. modulates substrate utilization mitochondrial respiration. Here we review experimental evidence supporting role regulation energy metabolism function.

Language: Английский

Citations

5
Energy substrate supplementation increases ATP levels and is protective to PD neurons DOI Creative Commons
Andrey Y. Vinokurov, Marina Yu. Pogonyalova,

Larisa Andreeva

et al.

Current Research in Pharmacology and Drug Discovery, Journal Year: 2024, Volume and Issue: 6, P. 100187 - 100187

Published: Jan. 1, 2024

Alteration of mitochondrial metabolism by various mutations or toxins leads to neurological conditions. Age-related changes in energy could also play the role a trigger for neurodegenerative disorders. Nonetheless, it is not clear if restoration ATP production supplementation brain cells with substrates be neuroprotective. Using primary neurons and astrocytes, familial forms disorders we studied whether improve stimulate production, increased levels protect against glutamate excitotoxicity neurodegeneration. We found that several substrates, combination thereof, TCA cycle cellular respiration, oxidative phosphorylation resulted an increase NADH level membrane potential led astrocytes. Subsequently, these were protected deprivation during ischemia excitotoxicity. Provision Parkinson's disease prevented triggering cell death. Thus, can neuroprotective A succinate salt choline nicotinamide provided best results.

Language: Английский

Citations

4
Carotid Endarterectomy Ameliorates Cognitive Impairment in Clinical and Experimental Unilateral Carotid Artery Stenosis DOI Creative Commons
Yijun Cheng, Bin Chen, Miao Zhang

et al.

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Background Carotid endarterectomy (CEA) is widely used to treat carotid artery stenosis (CAS). However, the effects of CEA on unilateral CAS‐induced cognitive impairment and underlying mechanism remain poorly understood. Methods Results Thirteen patients diagnosed with severe CAS underwent pre‐ post‐CEA assessments, including 18 fluoro‐2‐deoxy‐ d ‐glucose positron emission tomography/magnetic resonance imaging, routine blood tests before after CEA. Unilateral common occlusion ligation release (reperfusion) surgeries were performed in mice mimic Cognitive function, cerebral flow, white matter damage evaluated using Morris water maze test, Doppler flowmetry, laser‐speckle diffusion tensor Luxol fast blue staining, transmission electron microscopy, western blot assays post reperfusion. Genomic sequencing was explore potential mechanism. significantly enhanced Montreal Assessment scores preoperative impairment. Moreover, led notable improvements energy metabolism, integrity, while concurrently reducing inflammation. In mouse model, reperfusion surgery alleviated deficits, increased following occlusion. Furthermore, transcriptional surveys have revealed substantial alterations upregulation Nrf2 signaling metabolic pathways, coupled inhibition neuroinflammation, cellular communication, immune cell population Conclusions ameliorated dysfunction by improving functional structure. These beneficial may be attributed their antioxidant anti‐inflammatory properties.

Language: Английский

Citations

0