Ferroptosis role in complexity of cell death: unrevealing mechanisms in Parkinson’s disease and therapeutic approaches

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Language: Английский

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Mechanisms and early efficacy data of caloric restriction and caloric restriction mimetics in neurodegenerative disease

Neuroscience, Journal Year: 2025, Volume and Issue: 567, P. 235 - 248

Published: Jan. 5, 2025

Language: Английский

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Therapeutic approaches targeting aging and cellular senescence in Huntington's disease

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(10)

Published: Oct. 1, 2024

Huntington's disease (HD) is a devastating neurodegenerative that manifested by gradual loss of physical, cognitive, and mental abilities. As the advances, age has major impact on pathogenic signature mutant huntingtin (mHTT) protein aggregation. This review aims to explore intricate relationship between aging, mHTT toxicity, cellular senescence in HD. Scientific data interplay mHTT, HD were collected from several academic databases, including PubMed, Google Scholar, Google, ScienceDirect. The search terms employed "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," "CELLULAR SENESCENCE." Additionally, gather information molecular mechanisms potential therapeutic targets, was extended include relevant such as "DNA DAMAGE," "OXIDATIVE STRESS," "AUTOPHAGY." According research, aging leads worsening pathophysiology through some processes. result accumulation, promoted, which causes DNA damage, oxidative stress, decreased autophagy, increased inflammatory responses. Pro-inflammatory cytokines other substances are released senescent cells, may worsen neuronal damage course disease. It been shown treatments directed at these pathways reduce symptoms enhance longevity experimental animals, pointing new possibility treating condition. Through their amplification harmful effects play crucial roles development Comprehending interplays creates novel opportunities for measures targeted alleviating enhancing patients' quality life.

Language: Английский

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Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular Ca2+ Levels and ROS/p53/p38 Axis

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 46 - 46

Published: Jan. 3, 2025

Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated effects myricitrin (1–20 μg/mL) on copper-induced toxicity (0.5 mM CuSO4) neuroblastoma SH-SY5Y line. At non-toxic concentrations, exacerbated copper’s toxic effects. The myricitrin-induced decrease survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase lower GSH/GSSG ratio. In combination copper, activated caspase-3/7, promoted nuclear chromatin changes, compromised membrane integrity. protein level, upregulated p53 PUMA expression. were alleviated by p38 inhibitor SB203580, intracellular calcium chelator BAPTA-AM, NMDA receptor blocker MK-801, highlighting significant role ROS/p53/p38 axis death critical involvement ions apoptosis atomic force microscopy used assess surface morphology nanomechanical properties cells, revealing changes following treatment. research highlights potential emphasizes need caution when considering flavonoid supplementation conditions elevated levels.

Language: Английский

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Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases

Genes, Journal Year: 2025, Volume and Issue: 16(2), P. 135 - 135

Published: Jan. 24, 2025

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and amyotrophic lateral sclerosis (ALS), represent a growing societal challenge due to their irreversible progression significant impact on patients, caregivers, healthcare systems. Despite advances in clinical imaging-based diagnostics, these diseases are often detected at advanced stages, limiting the effectiveness of therapeutic interventions. Recent breakthroughs genomic transcriptomic technologies, including whole-genome sequencing, single-cell RNA sequencing (scRNA-seq), CRISPR-based screens, have revolutionized field, offering new avenues for early diagnosis personalized prognosis. Genomic approaches elucidated disease-specific genetic risk factors molecular pathways, while studies identified stage-specific biomarkers that correlate with severity. Furthermore, genome-wide association (GWAS), polygenic scores (PRS), spatial transcriptomics enabling stratification patients based profiles prognostic trajectories. Advances functional genomics uncovered actionable targets, ATXN2 ALS TREM2 AD, paving way tailored strategies. achievements, challenges remain translating discoveries into practice heterogeneity complexity neurodegenerative pathophysiology. Future integration technologies holds promise transforming diagnostic paradigms, hope improved patient outcomes precision medicine approaches.

Language: Английский

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Surface-enhanced Raman scattering for the detection of biomarkers of neurodegenerative diseases: A review

TrAC Trends in Analytical Chemistry, Journal Year: 2025, Volume and Issue: 185, P. 118173 - 118173

Published: Feb. 3, 2025

Language: Английский

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Future Perspectives of NMDAR in CNS Disorders

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 877 - 877

Published: Feb. 14, 2025

Neurodegenerative diseases such as Alzheimer's and Parkinson's are among the leading causes of physical cognitive disability across globe. Fifty million people worldwide suffer these diseases, that number is expected to rise population ages. Ictus another pathology also courses with neurodegeneration a cause mortality long-term in developed countries. Schizophrenia not common other mental disorders, affecting approximately 24 worldwide. All disorders have still there an effective pharmacological treatment cure them. The N-methyl-D-aspartate (NMDA) receptor (NMDAR) has attracted attention potential therapeutic target due its important role learning memory implication excitotoxicity processes. Some drugs targeting NMDARs already being used treat symptoms central nervous system (CNS). Here, we aim review implications NMDAR CNS pathologies, target, future perspectives for developing new treatments focused on receptors.

Language: Английский

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Editorial: Neuroinflammation and neurodegenerative diseases

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 14, 2025

Neurodegenerative diseases, characterized by the progressive loss of neuronal structure and function, are among most devastating health challenges modern era (1). Disorders such as Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS) share few common pathological hallmarks: neurodegeneration, neuroinflammation, impaired brain integrity/connectivity (2). This complex interplay immune-mediated responses in central nervous system (CNS) integrity has emerged a pivotal contributor to damage progression (3). The growing body research on this topic underscores importance unraveling mechanisms neuroinflammation restoring homeostasis, which will pave way for innovative therapeutic strategies.This Research Topic, titled Neuroinflammation Diseases, comprises fourteen insightful contributions from leading researchers. Collectively, these studies explore molecular cellular underpinnings diagnostic potential biomarkers, promising avenues. Additional insights provided how peripherally-derived risk factors [such type 2 diabetes mellitus (T2DM), osteoarthritis, Coronavirus Disease 2019 (COVID-19)] can have an impact integrity/neuroinflammation. editorial highlights key themes findings presented collection.Unraveling Molecular MechanismsAmong variety neurodegenerative phenotypes, understanding basis is crucial identifying targets. Several collection shed light mechanisms. For instance, role Calcitonin Gene Related Peptide (CGRP) synucleinopathies offers into mediators neuroinflammation(4). Likewise, study α-Synuclein-mediated mitochondrial translocation cofilin-1 elucidates dysfunction oxidative stress intertwined PD pathology (5). reciprocal roles retro-elements regulating memory immunity, discussed one article, further deepen our genetic epigenetic neurodegeneration (6). Such underscore intricate networks driving neuroinflammatory processes.Inflammatory Biomarkers DiagnosticsThe pursuit reliable biomarkers early diagnosis monitoring remains cornerstone research. values plasma cell-free nuclear DNA (cf-nDNA) (cf-mtDNA) atrophy, explored study, highlight promise liquid biopsy approaches (7). Another associates higher serum lipoprotein-associated phospholipase A₂ (Lp-PLA2) levels with cognitive impairment patients, emphasizing systemic inflammation markers CNS diseases (8).Many peripheral causes trigger neuroinflammation. example, comprehensive magnetic resonance imaging (MRI) assessments revealing subtle non-hospitalized post-COVID patients extend discussion post-viral syndromes (9). Similarly, Zhou et al. observed significant abnormalities connectivity topology large functional T2DM patients. Liu positive correlation between osteoarthritis disease. relevance broader contexts, including long-term sequelae infectious, metabolic, other degenerative diseases. Therapeutic Approaches InterventionsTargeted therapies mitigate hold transformative neuroprotective effects aqueous extract Swietenia macrophylla leaf murine model (10), along mood-enhancing properties diethyl butylmalonate 5×familial (FAD) mice, exemplify novel pharmacological interventions (11).Non-pharmacological also show promise. regulation microglia through physical exercise, highlighted lifestyle modifications adjunctive (12). These align efforts identify holistic accessible options.Neuroprotective StrategiesPreserving amidst primary objective sleep, anxiety, depression traumatic injury outcomes, analyzed another contribution, psychosocial dimensions neuroprotection (13).Additionally, spatiotemporal consistency analysis cerebral small vessel via resting-state MRI (rs-fMRI) provides window vascular need integrated neurovascular protective strategies (14). Looking AheadThis represents step forward specific emphasis metabolic condition, (Fig. 1). bridge gaps basic science translational research, providing roadmap future investigations. By actionable targets validating interventions, lay groundwork solutions medicine's pressing challenges.We gratitude all contributors their invaluable encourage continued interdisciplinary collaboration field. Together, we aspire translate scientific advances tangible benefits families, ultimately transforming landscape management.

Language: Английский

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Brain-computer interfaces in neurorehabilitation for central nervous system diseases: Applications in stroke, multiple sclerosis and Parkinson's disease

SANAMED, Journal Year: 2025, Volume and Issue: 00, P. 75 - 75

Published: Jan. 1, 2025

Brain-computer interfaces (BCIs) represent an innovative approach to neurorehabilitation for neurological conditions, particularly stroke, multiple sclerosis, and Parkinson's disease. This paper provides a comprehensive analysis of current BCI applications, technological developments, clinical outcomes in these conditions. Recent advances electroencephalography-based BCIs have demonstrated promising results, with classification accuracies exceeding 90% stroke rehabilitation comparable performance sclerosis Meta-analyses trials (n=235) indicate significant motor function improvements , standardized mean differences 0.79 upper limb assessment scores compared conventional therapy. Disease-specific challenges necessitate tailored approaches, while hybrid systems combining signal types integration virtual reality or robotic assistance enhance therapeutic potential. The development portable, home-based offers increased therapy intensity but raises concerns about remote monitoring safety protocols. review synthesizes evidence supporting applications highlights critical areas future research, including cognitive optimization the standardization outcome measures cross-condition comparison.

Language: Английский

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Peptide Fraction from Naja mandalayensis Snake Venom Showed Neuroprotection Against Oxidative Stress in Hippocampal mHippoE-18 Cells but Not in Neuronal PC12 Cells

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 277 - 277

Published: Feb. 26, 2025

Functional characterization of peptide fraction (PF) from snake venom has provided novel opportunities to investigate possible neuroprotective compounds relevant pharmaceuticals. This study was performed the PF-mediated neuroprotection obtained Naja mandalayensis venom, a member Elapidae family, using two neuronal cell lines, undifferentiated PC12 and differentiated mHippoE-18, in response H2O2-induced oxidative stress. Cells were pre-treated for 4 h with PF (10, 1, 0.01, 0.001 μg mL-1), thereafter exposed H2O2 (0.5 mmol L-1) 20 h. Then, stress markers label-free differential proteome strategy analyzed understand effects PF. In cells, showed no against mHippoE-18 at 0.01 mL-1 increased viability metabolism cells neurotoxicity, reducing reactive oxygen species (ROS) generation. Interestingly, also exhibited substantial reduction baseline ROS levels compared control, indicating that could have antioxidant features. The comparative proteomic profiling identified 53 proteins expression related action, catalysis, molecular function regulators, structural molecule activity, translation regulatory ATP, binding. + group indicated protein is 6% upregulated, 4% downregulated, 94% unchanged group. Three significant upregulated group, including elongation factor 2 (P58252), proteasome subunit alpha type (E9Q0X0), E2 ubiquitin-conjugating enzyme (A0A338P786), suggested happens through translational regulation degradation defective via complex. Additionally, changed metabolism, synthesis, synaptic intracellular transport, suggesting contains rich mixture bioactive peptides interest pharmacologically. Overall, this offers new evaluating whether PF's features specific are maintained neurodegenerative disease drug development processes.

Language: Английский

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