Synaptic Function and Dysfunction: New Frontiers in CNS Disorders

Journal of Neuroscience Research, Год журнала: 2025, Номер 103(4)

Опубликована: Апрель 1, 2025

Central nervous system (CNS) disorders, such as Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), and migraines, rank among the most prevalent concerning conditions worldwide. Despite ongoing research, pathophysiology of these disorders remains incompletely understood, primarily due to their complex etiology. Current pharmacological treatments mainly focus on alleviating symptoms rather than addressing underlying causes diseases. CNS are marked by impairments in neurocognitive neuromuscular functions, cognitive processes like learning memory. This deterioration not only impacts quality life affected individuals but also places a significant burden families. Neuroplasticity is key property that enables brain repair functional recovery. However, neuroplasticity often compromised. Neuroplasticity, which regulated gene expression, modulated environmental factors epigenetic mechanisms, thereby reshaping neuronal networks response various biological stimuli function. Importantly, plays critical role repairing brain, especially context neurodegenerative diseases, where damaged neurons can reorganize re-establish lost functions. Targeting mechanisms holds potential for developing therapeutic interventions improve treatment outcomes prevent disorders. A deeper understanding neurological diseases could open new avenues enhancing patient life. review aims provide comprehensive overview synaptic function disrupted

Язык: Английский

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Structural characterization and anti-neuroinflammatory activity of polysaccharides isolated from the leaves of Perilla frutescens

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 143029 - 143029

Опубликована: Апрель 1, 2025

Язык: Английский

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The Ferroptosis–Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation

Antioxidants, Год журнала: 2025, Номер 14(5), С. 613 - 613

Опубликована: Май 20, 2025

Emerging evidence links ferroptosis–mitochondrial dysregulation to depression pathogenesis through an oxidative stress–energy deficit–neuroinflammation cycle driven by iron overload. This study demonstrates that accumulation initiates ferroptosis via Fenton reaction-mediated lipid peroxidation, compromising neuronal membrane integrity and disabling the GPx4 antioxidant system. Concurrent mitochondrial complex I/IV dysfunction impairs ATP synthesis, creating AMPK/mTOR signaling imbalance calcium dyshomeostasis synergistically impair synaptic plasticity. Bidirectional crosstalk emerges: peroxidation derivatives oxidize cardiolipin, while ROS overproduction activates ACSL4 amplify ferroptotic susceptibility, forming a self-reinforcing neurodegenerative loop. Prefrontal–hippocampal metabolomics reveal paradoxical metabolic reprogramming with glycolytic compensation suppressing biogenesis (via PGC-1α/TFAM downregulation), trapping neurons in bioenergetic crisis. Clinical data further show microglial M1 polarization cGAS-STING activation sustains neuroinflammation IL-6/TNF-α release. We propose “ferroptosis–mitochondrial fragmentation–metabolic maladaptation” triad as mechanistic subtyping criteria for depression. Preclinical validation shows combinatorial therapy (iron chelators + SIRT3 agonists) rescues viability restoring energy flux. work shifts therapeutic paradigms from monoaminergic targets toward multimodal strategies addressing homeostasis, organelle dynamics, vulnerability—a framework significant implications developing neuroprotective antidepressants.

Язык: Английский

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Reversing Epigenetic Dysregulation in Neurodegenerative Diseases: Mechanistic and Therapeutic Considerations

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4929 - 4929

Опубликована: Май 21, 2025

Epigenetic dysregulation has emerged as an important player in the pathobiology of neurodegenerative diseases (NDDs), such Alzheimer’s, Parkinson’s, and Huntington’s diseases. Aberrant DNA methylation, histone modifications, dysregulated non-coding RNAs have been shown to contribute neuronal dysfunction degeneration. These alterations are often exacerbated by environmental toxins, which induce oxidative stress, inflammation, genomic instability. Reversing epigenetic aberrations may offer avenue for restoring brain mechanisms mitigating neurodegeneration. Herein, we revisit evidence suggesting ameliorative effects modulators toxin-induced models NDDs. The restoration normal gene expressions, improvement function, reduction pathological markers deacetylase (HDAC) methyltransferase (DNMT) inhibitors demonstrated preclinical Encouragingly, clinical trials Alzheimer’s disease (AD), HDAC caused improvements cognition memory. Combining these beneficial with neuroprotective agents clearance misfolded amyloid proteins synergistic benefits. Reinforced emerging methods more effective brain-specific delivery, reversibility, safety considerations, anticipated minimize systemic toxicity yield favorable outcomes In summary, although still their infancy, integrated strategy address multifactorial nature NDDs, altering therapeutic landscape.

Язык: Английский

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A brief review of ALS from an immunological perspective with potential immunotherapy options

Discover Immunity., Год журнала: 2025, Номер 2(1)

Опубликована: Май 29, 2025

Язык: Английский

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Innovative approaches for the treatment of stroke: a recent update

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Май 29, 2025

Язык: Английский

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From genetic roots to recent advancements in gene therapy targeting amyloid beta in Alzheimer’s disease

Reviews in the Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Май 30, 2025

Abstract Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders. The pathological hallmarks AD are amyloid-beta (Aβ) plaques and tau protein tangles, which cause neurodegeneration lead to cognitive decline. distinguished role Aβ in onset disease, especially familial AD, alongside genetic complexity underscores need for precise targeted interventions targeting Aβ. This review first highlights amyloidogenic non-amyloidogenic pathways inflammatory mechanisms contributing accumulation. It also introduces variants such as amyloid precursor (APP), presenilin (PSEN1), PSEN2, Apolipoprotein E (APOE) molecular cellular involved pathology. Then, gene therapy techniques discussed their potential target either directly by inhibiting its production or enhancing degradation indirectly APOE, pathways, neurotrophic factors. While these approaches show significant preclinical promise, challenges timing, safety, delivery across blood–brain barrier persist further investigation.

Язык: Английский

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Future prospects of targeted drug delivery

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 377 - 402

Опубликована: Янв. 1, 2025

Язык: Английский

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Understanding Headaches Attributed to Cranial and/or Cervical Vascular Disorders: Insights and Challenges for Neurologists

Pain and Therapy, Год журнала: 2024, Номер 13(6), С. 1429 - 1445

Опубликована: Окт. 13, 2024

In recent decades, cranial and cervical vascular disorders have become major global health concerns, significantly impacting patients, families, societies. Headache is a prevalent symptom of these diseases can often be the initial, primary, or sole manifestation. The intricate relationship between headaches cranial/cervical poses diagnostic therapeutic challenge, with underlying mechanisms remaining largely elusive. Understanding this association crucial for early diagnosis, prevention, intervention such conditions. This review aims to provide comprehensive overview clinical features potential pathogenesis attributed reference disease management basis pathological mechanisms.

Язык: Английский

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The Improvement Effects of Sika Deer Antler Protein in an Alzheimer's Disease Mouse Model via the Microbe–Gut–Brain Axis

Food Science & Nutrition, Год журнала: 2024, Номер 13(1)

Опубликована: Дек. 30, 2024

ABSTRACT Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The interplay between intestinal microbiota and metabolites believed to influence brain function pathogenesis conditions through microbe–gut–brain axis. Sika deer antler protein possesses neuroprotective properties; however, precise mechanism by which it improves AD remains unclear. ameliorated in vivo activating phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2–related 2 (Nrf2) signaling pathway. metabolome tissues contents were tested analyzed according microbe‐gut‐brain theory. increased beneficial bacterial levels decreased harmful levels. Correlation analyses using gut flora–metabolomics pathway ultimately revealed that sika modulated tract bi‐directionally via tyrosine metabolism pathway, thereby establishing connection within Kyoto Encyclopedia Genes Genomes (KEGG) analysis differential metabolite targets DAP4 group showed enriched pathways mainly included PI3K/AKT, was consistent with findings pharmacodynamic mechanisms observed experiments. This suggests may be involved interactions improve PI3K/AKT/Nrf2 These add our understanding axis facilitated offer novel insights for further research on alleviating AD.

Язык: Английский

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