Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 2, 2024

Abstract Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation resident immune cells brain and penetration peripheral cells. These inflammatory processes facilitate deposition amyloid-beta (Aβ) plaques abnormal hyperphosphorylation tau protein. Managing neuroinflammation to restore homeostasis decrease neuronal damage therapeutic approach for AD. One way achieve this through exercise, which can improve function protect against neuroinflammation, oxidative stress, synaptic dysfunction in AD models. The neuroprotective impact exercise regulated various molecular factors that be activated same as administration their mimetics. Recent evidence has proven some mimetics effective alleviating AD, and, additionally, they are helpful alternative option patients who unable perform regular physical manage neurodegenerative disorders. This review focuses on current state knowledge mimetics, including efficacy, regulatory mechanisms, progress, challenges, limitations, future guidance application therapy.

Language: Английский

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Unveiling the potential of estrogen: Exploring its role in neuropsychiatric disorders and exercise intervention

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107201 - 107201

Published: May 3, 2024

Neuropsychiatric disorders shorten human life spans through multiple ways and become major threats to health. Exercise can regulate the estrogen signaling, which may be involved in depression, Alzheimer's disease (AD) Parkinson's (PD), other neuropsychiatric as well their sex differences. In nervous system, is an important regulator of cell development, synaptic brain connectivity. Therefore, this review aimed investigate potential system exercise intervention better understand its specific. exert a protective effect regulating expression receptors, are neuroprotection, neurodevelopment, neuronal glucose homeostasis. These processes mediated by downstream factors including N-myc regulatory gene 2 (Ndrg2), serotonin (5-HT), delta like canonical Notch ligand 1 (DLL1), NOD-like receptor thermal protein domain associated 3 (NLRP3), etc. addition, act on response element (ERE) fragment genes estrogenic β-amyloid precursor cleavase (BACE1). However, there few studies relationship between exercise, signaling pathway, disorders. Hence, we how mediates mechanism We aim provide theoretical perspective for affecting female health support design prescriptions.

Language: Английский

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Advancing Alzheimer’s Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2531 - 2531

Published: Oct. 27, 2023

Alzheimer’s disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including misfolding of tau protein and amyloid beta (Aβ) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating exploration therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aβ aggregates, minimizing formation neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating improving functionality neurovascular unit (NVU). Overall, neuroprotective are not singular, but multi-targets. Numerous studies have investigated physical exercise’s potential in both AD patients animal models, employing various protocols elucidate underlying neurobiological effects. The objective this review analyze neurological these models compare them conducted patients. By translating findings from different approaches, aims identify opportune, specific, personalized windows, thus advancing research use

Language: Английский

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GSK3-Driven Modulation of Inflammation and Tissue Integrity in the Animal Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8263 - 8263

Published: July 29, 2024

Nowadays, GSK3 is accepted as an enzyme strongly involved in the regulation of inflammation by balancing pro- and anti-inflammatory responses cells organisms, thus influencing initiation, progression, resolution inflammatory processes at multiple levels. Disturbances within its broad functional scope, either intrinsically or extrinsically induced, harbor risk profound disruptions to regular course immune response, including formation severe inflammation-related diseases. Therefore, this review aims summarizing contextualizing current knowledge derived from animal models further shape our understanding GSK3α β their roles process occurrence tissue/organ damage. Following a short recapitulation structure, function, GSK3, we will focus on lessons learned GSK3α/β knock-out knock-in/overexpression models, both conventional conditional, well variety (predominantly rodent) disease reflecting defined pathologic conditions with significant proportion tissue injury. In summary, literature suggests that acts crucial switch driving pro-inflammatory destructive contributes significantly pathogenesis inflammation-associated

Language: Английский

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Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 223, P. 111280 - 111280

Published: Feb. 25, 2025

The impairment of cognitive function has been associated with Alzheimer's disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective TREM2 synaptic this phenomenon. Here, we aim explore whether physical exercise pretreatment alters Aβ-induced recognition memory structural plasticity within hippocampus AD rats. METHODS：: In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), (AD 4 weeks and (Exe+AD blank (Exercise 13). Four treadmill intervention was performed, model established intra-cerebroventricular injection (ICV) Aβ1-42 protein. After 3 weeks, also conducted novel object test evaluate behavior assessment. Golgi staining transmission electron microscopy used morphology ultrastructure neurons. Western blotting measure expression hippocampal proteins. Extracellular neurotransmitters detected microdialysis coupled high-performance liquid chromatography. 2, 33 SD three 11), AAV-Control (AAV-Control+Exe+AD AAV-TREM2 (AAV-TREM2 +Exe+AD 11). Stereotactic intracerebral bilateral performed achieve microglial down-expression using adeno-associated virus (AAV) CD68 promoter. Aβ injection, all received molecular experiment, which same experiment 2. Novel index significantly decreased, western blot demonstrate that protein decreased (P < 0.001). But reversed phenomenon(P addition, compared Con neuron from Exe+AD exhibited more complex branching pattern 0.05). And impaired observed group. Hippocampal synaptic-related (SYX, SYP, GAP43, PSD95) neurotransmitter (DA, Glu, GABA) 0.01) neuroprotection can be found are inhibition injury activate when blockade reduced brain protective rat model, including increased damage neuronal dendritic complexity, ultrastructure, decrease synapses-related protein, typical neurotransmitter. Treadmill facilitated acquisition via TREM2-mediated an model.

Language: Английский

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Impact of Diet and Exercise on Mitochondrial Quality and Mitophagy in Alzheimer's disease

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102734 - 102734

Published: March 1, 2025

Language: Английский

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Neuroinflammation—A Crucial Factor in the Pathophysiology of Depression—A Comprehensive Review

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 502 - 502

Published: March 30, 2025

Depression is a multifactorial psychiatric condition with complex pathophysiology, increasingly linked to neuroinflammatory processes. The present review explores the role of neuroinflammation in depression, focusing on glial cell activation, cytokine signaling, blood-brain barrier dysfunction, and disruptions neurotransmitter systems. article highlights how inflammatory mediators influence brain regions implicated mood regulation, such as hippocampus, amygdala, prefrontal cortex. further discusses involvement hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, kynurenine pathway, providing mechanistic insights into chronic inflammation may underlie emotional cognitive symptoms depression. bidirectional relationship between depressive emphasized, along peripheral immune responses systemic stress. By integrating molecular, cellular, neuroendocrine perspectives, this supports growing field immunopsychiatry lays foundation for novel diagnostic biomarkers anti-inflammatory treatment approaches Further research holds promise developing more effective personalized interventions individuals suffering from

Language: Английский

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Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase

BMC Neuroscience, Journal Year: 2025, Volume and Issue: 26(1)

Published: April 28, 2025

Spinal cord injury is followed by glial scar formation, which was long seen mainly as a physical barrier preventing axonal regeneration. Glial astrocytes lead to formation and produce inhibitory factors prevent axons from growing through the scar, while inhibiting conversion of reactive into scar-forming may represent an ideal treatment for CNS injury. Exercise non-invasive effective therapeutic intervention clinical rehabilitation spinal However, its precise mechanisms still need be continuously explored. 30 rats were randomly assigned three groups (Sham, SCI, SCI + BWSTT; n = 10 per group). In this study, we employed BBB scales gait analysis system examine behavioral functions in each group. Furthermore, utilized immunoblotting tissue at site, addition histological staining immunofluorescence staining, explore aggregation regeneration group rats. Our results revealed that hindlimb motor function significantly improved after sustained subacute period BWSTT, accompanied promotion repair nerve Subsequent showed diminished astrocyte reactivity region surrounding well reduced expression distribution collagen fibers near lesion BWSTT. Additionally, significant decrease MMP-2/9, closely related migration, observed vicinity lesions. study demonstrates BWSTT during phase can effectively reduce scarring overgrowth, thereby facilitating functional recovery SCI.

Language: Английский

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Intelligence, brain structure, dendrites, and genes: genetic, epigenetic and the underlying of the quadruple helix complexity

Neuroscience & Biobehavioral Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 106212 - 106212

Published: May 1, 2025

Language: Английский

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Aerobic exercise attenuates abnormal myelination and oligodendrocyte differentiation in 3xTg-AD mice

Experimental Gerontology, Journal Year: 2023, Volume and Issue: 182, P. 112293 - 112293

Published: Sept. 22, 2023

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function neurons as well myelin sheaths. Accumulated evidence shows that aerobic type exercise can enhance neuroplasticity mouse models AD. However, whether how affect sheath repair neuroprotection AD remains unclear. In this study we tested hypotheses 1) structural 3xTg-AD mice would be related to abnormalities oligodendrocyte lineage cells, resulting impaired learning memory, 2) a 6-month intervention have beneficial effects on such alterations. Two-month-old male were randomly assigned control (AC) or an (AE) group, age-matched C57BL/6;129 also normal (NC) (NE) with n = 12 each group. Mice groups trained motor-drive treadmill, 60 min per day, 5 days week for 6 months. Cognitive was assessed at end period. Then, brain specimens obtained assessments morphological cell changes. The results electron microscopy showed ultrastructure demonstrated higher percentage loose granulated around axons temporal lobe AC, compared NC along greater cognitive dysfunction 8-months age. These differences accompanied by significantly basic protein (MBP) expression less neuron-glial antigen-2 (NG2) mRNA levels NC. there no significant between-group G-ratio (the ratio axon diameter plus diameter) 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) levels. ameliorated deterioration appeared keep components precursor cells stabilized, decrease MBP protein, increase NG2 AE Therefore, lesions, abnormal differentiation oligodendrocytes general mice, providing further insights into role management neurodegeneration maintaining intact myelination.

Language: Английский

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