Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102357 - 102357

Published: June 1, 2024

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due global demographic changes. NDs mainly represented by degeneration/loss of neurons, which is primarily accountable severe mental illness. This neuronal degeneration leads many neuropsychiatric problems permanent disability an individual. Moreover, tight junction brain, blood-brain barrier (BBB)has protective feature, functioning as biological that can prevent medicines, toxins, foreign substances from entering brain. However, delivering any medicinal agent brain (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) enormously challenging. There approved therapies address NDs, but most them only help treat associated manifestations. The available have failed control progression certain factors, i.e., BBB drug-associated undesirable effects. extremely complex pathology, with pathogenic mechanisms involved initiation progression; thereby, limited survival rate has been observed ND patients. Hence, understanding exact mechanism behind crucial developing alternative approaches improving patients' rates. Thus, present review sheds light on different cellular novel therapeutic their clinical relevance, will assist researchers alternate strategies limitations conventional therapies. current work offers scope into near future improve approach NDs.

Language: Английский

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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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Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications

Intelligent Pharmacy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Treadmill Exercise Modulates Intestinal Microbes and Suppresses LPS Displacement to Alleviate Neuroinflammation in the Brains of APP/PS1 Mice

Nutrients, Journal Year: 2022, Volume and Issue: 14(19), P. 4134 - 4134

Published: Oct. 5, 2022

Neuroinflammation occurs throughout the pathogenesis of Alzheimer's disease (AD). Here, we investigated effects treadmill exercise on neuroinflammation in APP/PS1 transgenic AD mice and potential involvement microbe-gut-brain axis (MGB) mechanisms based growing evidence that AD's is correlated with a deterioration function gut microbiota. were subjected to 12 weeks exercise, followed by spatial memory tests. After behavioral study, amyloid (Aβ) pathology, microbes metabolites, bacterial lipopolysaccharide (LPS) displacement, degree analyzed. We found this strategy enriched microbial diversity alleviated brain. Notably, led reductions pathogenic bacteria such as intestinal Allobaculum, increases probiotic Akkermansia, increased levels intestine-brain barrier proteins, attenuated LPS displacement. These results suggest prolonged can effectively modulate thereby reduce displacement ultimately alleviate AD-related neuroinflammation.

Language: Английский

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Establishing Co-Culture Blood–Brain Barrier Models for Different Neurodegeneration Conditions to Understand Its Effect on BBB Integrity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5283 - 5283

Published: March 9, 2023

The blood-brain barrier (BBB) is a functional interface that provides selective permeability, protection from toxic substances, transport of nutrients, and clearance brain metabolites. Additionally, BBB disruption has been shown to play role in many neurodegenerative conditions diseases. Therefore, the aim this study was establish functional, convenient, efficient vitro co-cultured model can be used for several physiological related disruption. Mouse brain-derived endothelial (bEnd.3) astrocyte (C8-D1A) cells were on transwell membranes an intact model. its effects different neurological diseases stress conditions, including Alzheimer's disease (AD), neuroinflammation, obesity, have examined by transendothelial electrical resistance (TEER), fluorescein isothiocyanate (FITC) dextran, tight junction protein analyses. Scanning electron microscope images showed evidence end-feet processes passing through membrane transwell. Moreover, effective properties TEER, FITC, solvent persistence leakage tests when compared mono-cultured immunoblot results expression proteins such as zonula occludens-1 (ZO-1), claudin-5, occludin-1 enhanced co-culture. Lastly, under structural integrity decreased. present demonstrated mimicked BBB's and, similar damages. convenient experimental tool investigate wide range BBB-related pathological studies.

Language: Английский

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Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 104 - 104

Published: Jan. 15, 2025

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of wide range brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) cause neuroinflammation, alter function, accelerate disease development. Despite progress understanding these pathways, effective medicines targeting are still limited. Traditional anti-inflammatory immunomodulatory drugs peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to central nervous system (CNS), blood-brain barrier (BBB) unwanted systemic effects. This review highlights developing treatment techniques modifying cytokine-driven focusing on advances that selectively target critical involved pathology. Novel approaches, cytokine-specific inhibitors, antibody-based therapeutics, gene- RNA-based interventions, sophisticated drug delivery systems like nanoparticles, show promise with respect lowering neuroinflammation greater specificity safety. Furthermore, developments biomarker discoveries neuroimaging improving our ability monitor responses, allowing more accurate personalized regimens. Preclinical clinical trial data demonstrate therapeutic potential tailored techniques. However, significant challenges remain, across BBB reducing off-target As research advances, creation personalized, cytokine-centered therapeutics has therapy landscape illnesses, giving patients hope better results higher quality life.

Language: Английский

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Photobiomodulation Combined With Human Umbilical Cord Mesenchymal Stem Cells Modulates the Polarization of Microglia

Journal of Biophotonics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

ABSTRACT Neuroinflammation plays a key role in the development of neurodegenerative diseases, with microglia regulating this process through pro‐inflammatory M1 and anti‐inflammatory M2 phenotypes. Studies have shown that human umbilical cord mesenchymal stem cells (hUCMSCs) modulate neuroinflammation by secreting cytokines. Photobiomodulation (PBM), non‐invasive therapy, has demonstrated significant potential alleviating neuroinflammation. This study examines combined effects PBM hUCMSCs an vitro microglial inflammation model LPS‐induced mouse model. The results show PBM‐pretreated promoted polarization improved cognitive function mice downregulating Notch signaling pathway, suggesting promising new approach for treating diseases.

Language: Английский

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New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5383 - 5383

Published: March 11, 2023

Alzheimer’s disease (AD) is an incurable, progressive neurodegenerative disorder. AD a complex and multifactorial that responsible for 60–80% of dementia cases. Aging, genetic factors, epigenetic changes are the main risk factors AD. Two aggregation-prone proteins play decisive role in pathogenesis: β-amyloid (Aβ) hyperphosphorylated tau (pTau). Both them form deposits diffusible toxic aggregates brain. These biomarkers Different hypotheses have tried to explain pathogenesis served as platforms drug research. Experiments demonstrated both Aβ pTau might start processes necessary cognitive decline. The two pathologies act synergy. Inhibition formation has been old target. Recently, successful clearance by monoclonal antibodies raised new hopes treatments if detected at early stages. More recently, novel targets, e.g., improvements amyloid from brain, application small heat shock (Hsps), modulation chronic neuroinflammation different receptor ligands, microglial phagocytosis, increase myelination revealed

Language: Английский

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Combined Donepezil with Astaxanthin via Nanostructured Lipid Carriers Effective Delivery to Brain for Alzheimer’s Disease in Rat Model

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 4193 - 4227

Published: July 1, 2023

Introduction: Donepezil (DPL), a specific acetylcholinesterase inhibitor, is used as first-line treatment to improve cognitive deficits in Alzheimer's disease (AD) and it might have modifying effect. Astaxanthin (AST) natural potent antioxidant with neuroprotective, anti-amyloidogenic, anti-apoptotic, anti-inflammatory effects. This study aimed prepare nanostructured lipid carriers (NLCs) co-loaded donepezil astaxanthin (DPL/AST–NLCs) evaluate their vivo efficacy an AD-like rat model 30 days after daily intranasal administration. Methods: DPL/AST–NLCs were prepared using hot high-shear homogenization technique, vitro examined for physicochemical parameters evaluated. AD induction rats was performed by aluminum chloride. The cortex hippocampus isolated from the brain of biochemical testing histopathological examination. Results: showed z-average diameter 149.9 ± 3.21 nm, polydispersity index 0.224 0.017, zeta potential – 33.7 4.71 mV, entrapment efficiency 81.25 1.98% (donepezil) 93.85 1.75% (astaxanthin), sustained release both 24 h, spherical morphology transmission electron microscopy, they stable at 4– 8 2°C six months. Differential scanning calorimetry revealed that molecularly dispersed NLC matrix amorphous state. DPL/AST–NLC-treated significantly lower levels nuclear factor-kappa B, malondialdehyde, β-site amyloid precursor protein cleaving enzyme-1, caspase-3, beta (Aβ 1‑42 ), acetylcholinesterase, higher glutathione acetylcholine than untreated treated donepezil–NLCs. antioxidant, anti-acetylcholinesterase, anti-inflammatory, anti-apoptotic effects, resulting significant improvement cortical hippocampal histopathology. Conclusion: Nose-to-brain delivery promising strategy management AD. Keywords: disease, donepezil, astaxanthin, delivery,

Language: Английский

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Impact of levetiracetam on cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis caused by lipopolysaccharides in rats

Saudi Pharmaceutical Journal, Journal Year: 2023, Volume and Issue: 31(9), P. 101728 - 101728

Published: Aug. 3, 2023

Neuroinflammation is associated with the elevation of toxic proinflammatory mediators that promote neurodegeneration and subsequently affect cognition. Causes inflammation in neuronal cells are believed to initiate various neurodegenerative disorders, mainly Alzheimer's disease. Levetiracetam a second-generation antiepileptic drug. There evidence supporting memory-enhancing effect levetiracetam from numerous experimental clinical studies. Therefore, this research focused on finding its protective effects against lipopolysaccharides prompted cognitive impairment exploring possible mechanisms underlining their neuroprotection.Two doses (100 or 200 mg/kg) were administrated orally for 30 days. Additionally, four (250 µg/kg) lipopolysaccharide injected peripherally induce neurotoxicity. Behavioral tests carried out using maze models. At end tests, brain tissues collected biochemical evaluations. Cholinergic, neuroinflammatory, apoptosis, oxidative-related parameters analyzed homogenate explore action levetiracetam.In lipopolysaccharide-induced rats, indicated reduction (p < 0.01) transfer latency elevated plus-maze. An improvement novel familiar objects exploration time object recognition test. A rise 0.05) arm entries extended spent Y-maze In extension, levels acetylcholine 0.001), anti-inflammatory factors (transforming growth factor-β1; p 0.01 interleukin-10; 0.05), an antioxidant (catalase; rats after administration levetiracetam. contrast, inflammatory (cyclooxygenase-2; 0.05, nuclear factor kappa B; tumor necrosis factor-α; 0.01, interleukin-6 0.01), apoptosis inducers (BCL2-associated X protein; 0.05 Caspase-3 oxidative stress (malondialdehyde; considerably reduced rats.The collective results suggested may be able treat neuroinflammatory-related memory loss by enhancing cholinergic activity while reducing neuroinflammation, cellular stress.

Language: Английский

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