Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00525 - e00525

Published: Jan. 1, 2025

Language: Английский

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The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1208 - 1208

Published: Oct. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Language: Английский

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Role of Oxidative Stress in Blood–Brain Barrier Disruption and Neurodegenerative Diseases

Antioxidants, Journal Year: 2024, Volume and Issue: 13(12), P. 1462 - 1462

Published: Nov. 28, 2024

Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes

Language: Английский

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Astaxanthin-loaded brain-permeable liposomes for Parkinson’s disease treatment via antioxidant and anti-inflammatory responses

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Parkinson's disease is a neurodegenerative disorder characterized by cardinal motor symptoms resulting from the loss of dopaminergic neurons in substantia nigra pars compacta. Although current medications may alleviate its symptoms, remains incurable. Astaxanthin an antioxidant and anti-inflammatory agent; however, high susceptibility to oxidative degradation low aqueous solubility limit therapeutic efficacy. This study aimed improve pharmaceutical properties neuroprotective effects astaxanthin for treatment using lactoferrin-conjugated astaxanthin-loaded liposomes (Lf-ASX-LPs). We successfully formulated Lf-ASX-LPs with encapsulation efficiency (97.6%) favorable physical characteristics (diameter: 109.8 ± 1.1 nm; polydispersity index: 0.18 0.01; zeta potential: - 9.5 mV). Lf-functionalized demonstrated enhanced cellular uptake permeation Transwell® study, showing 16.7-fold higher internalization SH-SY5Y cells over 24 h than those without Lf conjugation. Additionally, functionalization brain penetration ability, as biodistribution nude mice, compared LPs In vitro, reduced cell 20.1% oxygen species 30.0%, ameliorated reduction mitochondrial membrane potential under 1-methyl-4-phenylpyridinium-induced toxicity 40.1%, extracellular nitric oxide levels lipopolysaccharide-induced 32.0%, indicating cytoprotective effects. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, resulted 5.0-, 3.1-, 5.6-fold increases dopamine levels, TH+ fiber density, neurons, respectively, restoring neuron damage. The developed formulation also alleviated behavioral impairment neuroinflammation, reducing astrocyte microglial activation striatum MPTP-treated animals. Thus, our represents promising strategy providing neuroprotection retarding progression.

Language: Английский

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Mitochondrial Dysfunction in Neurodegenerative Diseases

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 276 - 276

Published: Feb. 13, 2025

Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's Huntington's and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical pathological features, exhibit shared pathways leading to neuronal damage, all which are closely associated with mitochondrial dysfunction. The high metabolic requirements neurons make even minor deficiencies highly impactful, driving oxidative stress, energy deficits, aberrant protein processing. Growing evidence from genetic, biochemical, cellular investigations associates impaired electron transport chain activity disrupted quality-control mechanisms, such as mitophagy, the initial phases disease progression. Furthermore, overproduction reactive oxygen species persistent neuroinflammation can establish feedforward cycles that exacerbate deterioration. Recent research has increasingly focused on interventions aimed at enhancing resilience-through antioxidants, small molecules modulate balance fusion fission, or gene-based therapeutic strategies. Concurrently, initiatives identify dependable biomarkers seek detect changes prior manifestation overt symptoms. By integrating current body knowledge, this review emphasizes critical role preserving homeostasis viable approach. It also addresses complexities translating these findings into practice underscores potential innovative strategies designed delay potentially halt processes.

Language: Английский

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Hydrogen Sulfide and Gut Microbiota: Their Synergistic Role in Modulating Sirtuin Activity and Potential Therapeutic Implications for Neurodegenerative Diseases

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1480 - 1480

Published: Nov. 4, 2024

The intricate relationship between hydrogen sulfide (H2S), gut microbiota, and sirtuins (SIRTs) can be seen as a paradigm axis in maintaining cellular homeostasis, modulating oxidative stress, promoting mitochondrial health, which together play pivotal role aging neurodegenerative diseases. H2S, gasotransmitter synthesized endogenously by specific acts potent modulator of function protecting against damage. Through sulfate-reducing bacteria, microbiota influences systemic H2S levels, creating link health metabolic processes. Dysbiosis, or an imbalance microbial populations, alter production, impair function, increase heighten inflammation, all contributing factors diseases such Alzheimer’s Parkinson’s. Sirtuins, particularly SIRT1 SIRT3, are NAD+-dependent deacetylases that regulate biogenesis, antioxidant defense, inflammation. enhances sirtuin activity through post-translational modifications, sulfhydration, activate pathways essential for mitigating damage, reducing longevity. SIRT1, example, deacetylates NF-κB, pro-inflammatory cytokine expression, while SIRT3 modulates key enzymes to improve energy metabolism detoxify reactive oxygen species (ROS). This synergy is profoundly influenced the levels and, turn, impacts activation. microbiota–H2S–sirtuin also regulating neuroinflammation, plays central pathogenesis Pharmacological interventions, including donors sirtuin-activating compounds (STACs), promise these synergistically, providing novel therapeutic approach conditions. suggests diversity optimal have far-reaching effects on brain health.

Language: Английский

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From mitochondrial dysfunction to neuroinflammation in Parkinson’s disease: Pathogenesis and mitochondrial therapeutic approaches

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113015 - 113015

Published: Sept. 1, 2024

Language: Английский

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Newer Therapeutic Approaches in Treating Alzheimer’s Disease: A Comprehensive Review

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 5148 - 5171

Published: Feb. 3, 2025

Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative affecting mostly the elderly population. The main pathological features of AD are extracellular Aβ plaques generated by APP cleavage through amyloidogenic pathway, intracellular neurofibrillary tangles (NFT) resulting from hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, actual causes unknown, but several studies suggest hereditary mutations in PSEN1 -2, APOE4, APP, TAU genes major perpetrators. In order to understand etiology pathogenesis AD, various hypotheses proposed. These include following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, deficiency, gut dysbiosis. Currently approved therapeutic interventions donepezil, galantamine, rivastigmine, which cholinesterase inhibitors (ChEIs), memantine, N-methyl-d-aspartate (NMDA) antagonist. treatment strategies focus on only symptomatic management attenuating symptoms not regeneration neurons or clearance Tau. This review focuses pathophysiology, novel targets, disease-altering treatments such as α-secretase modulators, active immunotherapy, passive natural antioxidant products, nanomaterials, antiamyloid therapy, aggregation inhibitors, transplantation fecal microbiota stem cells, microtubule stabilizers that clinical trials still under investigation.

Language: Английский

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The Potential of cfDNA as Biomarker: Opportunities and Challenges for Neurodegenerative Diseases

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: March 13, 2025

Abstract Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS), and amyotrophic lateral (ALS), are characterized by the progressive gradual degeneration of neurons. The prevalence rates these disorders rise significantly with age. As life spans continue to increase in many countries, number cases is expected grow foreseeable future. Early precise diagnosis, along appropriate surveillance, continues pose a challenge. high heterogeneity neurodegenerative diseases calls for more accurate definitive biomarkers improve clinical therapy. Cell-free DNA (cfDNA), fragmented released into bodily fluids via apoptosis, necrosis, or active secretion, has emerged as promising non-invasive diagnostic tool various diseases. cfDNA can serve an indicator ongoing cellular damage mortality, neuronal loss, may provide valuable insights processes, progression, therapeutic responses. This review will first cover key aspects then examine recent advances its potential use biomarker disorders.

Language: Английский

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Natural products in neurodegenerative diseases: recent advances and future outlook

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 19, 2025

Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s are on the rise pose significant challenges due to lack of effective treatments. This review critically examines neuroprotective effects various natural products derived from plants, marine organisms, fungi. Natural have long been used in traditional medicine gaining attention modern drug discovery for their unique properties. The explains how these can protect neurons by influencing key biological pathways involved neurodegeneration. It discusses mechanisms including antioxidant effects, anti-inflammatory actions, modulation cellular signalling, support mitochondrial function. A systematic literature search was conducted minimize bias ensure rigorous study selection. Preclinical studies using animal models cell cultures show that secondary metabolites like polyphenols, alkaloids, terpenoids significantly reduce neuronal damage. Some clinical trials shown promising results. However, bioavailability, standardization, dosage must be addressed translate findings into practice. also evaluates potential synergy combining with conventional treatments, offering a complementary therapeutic approach. represent avenue developing innovative treatments neurodegenerative diseases. highlights research gaps proposes future directions. Future should focus overcoming existing refining improve efficacy safety settings. application knowledge has enhance quality life individuals affected

Language: Английский

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