npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)
Published: May 6, 2025
Language: Английский
Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)
Published: Jan. 19, 2025
Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to disorders. This review elucidates the complex interplay between peripheral and central components underlying pathology. Peripherally, systemic inflammation, gut dysregulation, dysfunction in organs including gut, liver, spleen adipose tissue influence brain function through neural molecular pathways. Within nervous system, aberrant microglial astrocytes activation, cytokine imbalances, compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, promoting neuronal injury. The crosstalk immunity creates vicious cycle exacerbating neuropathology. Unraveling these multifaceted immune-mediated provides insights into major disorder's pathogenic basis potential biomarkers targets. Modulating both responses represent promising multidimensional therapeutic strategy.
Language: Английский
Citations
5
Acta Neuropathologica Communications, Journal Year: 2022, Volume and Issue: 10(1)
Published: Aug. 22, 2022
Abstract Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, is needed for neuronal development, function, survival. Deficits in axonal have been detected at pre-symptomatic stages the SOD1 G93A TDP-43 M337V mouse models amyotrophic lateral sclerosis (ALS), suggesting that impairments this critical process are fundamental disease pathogenesis. Strikingly, ALS, fast motor neurons (FMNs) degenerate first whereas slow (SMNs) more resistant, a currently unexplained phenomenon. The main aim investigation was to determine effects brain-derived neurotrophic factor (BDNF) on vivo different α-motor neuron (MN) subtypes wild-type (WT) mice. We report despite displaying similar basal speeds, stimulation MNs with BDNF enhances trafficking signalling endosomes specifically FMNs. This BDNF-mediated enhancement also observed primary ventral horn cultures. However, FMNs display selective impairment symptomatic mice , refractory stimulation, phenotype embryonic neurons. Furthermore, upregulation classical non-pro-survival truncated TrkB p75 NTR receptors muscles, sciatic nerves, Schwann cells. Altogether, these data indicate cell- non-cell autonomous impaired MNs, thus identifying new key deficit ALS.
Language: Английский
Citations
42
Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 12(9)
Published: Sept. 1, 2023
Extracellular vesicles (EVs) play an important role in intercellular communication as carriers of signalling molecules such bioactive miRNAs, proteins and lipids. EVs are key players the functioning central nervous system (CNS) by influencing synaptic events modulating recipient neurons. However, specific neuron-to-neuron via is still not well understood. Here, we provide evidence that primary neurons uptake neuron-derived soma, dendrites, even dendritic spines, carry proteins. Neuron-derived increased spine density promoted phosphorylation Akt ribosomal protein S6 (RPS6), TrkB-signalling, without impairing neuronal network activity. Strikingly, exerted a trophic effect on challenged nutrient-deprived Altogether, our results place spotlight for plasticity modulation possible therapeutic tool to fight neurodegeneration.
Language: Английский
Citations
27
Nutrients, Journal Year: 2025, Volume and Issue: 17(4), P. 601 - 601
Published: Feb. 7, 2025
Recent studies have highlighted the neuroprotective effects of polyphenols, particularly their role in enhancing brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) activity. This study aimed to evaluate relationship between BDNF CREB levels cognitive performance individuals undergoing a polyphenol-rich dietary intervention. A randomized, crossover, double-blind, placebo-controlled clinical trial was conducted with 92 participants. The intervention involved daily intake an encapsulated concentrate fruit, vegetable, berry juice powders (Juice Plus+ Premium®) over two 16-week periods, separated by 4-week washout phase. Cognitive function assessed using Stroop Test, Trail Making Reynolds Intellectual Screening Test (RIST). plasma were measured ELISA. product significantly improved performance, as evidenced higher scores RIST, compared placebo. Additionally, notably elevated condition, indicating enhanced findings suggest that nutraceuticals can modulate neurobiological mechanisms underlying improvements, primarily through reduction oxidative stress regulation signaling pathways associated synaptic plasticity. These results support potential polyphenols promoting health preventing neurodegenerative diseases.
Language: Английский
Citations
2
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4271 - 4271
Published: April 30, 2025
The brain-derived neurotrophic factor (BDNF) has become one of the cornerstones neuropathology, influencing synaptic plasticity, cognitive resilience, and neuronal survival. Apart from its molecular biology, BDNF is a powerful target for transformative benefit in precision medicine, leading to innovative therapeutic approaches neurodegenerative psychiatric diseases like Alzheimer's disease (AD), Parkinson's (PD), major depressive disorder (MDD), post-traumatic stress (PTSD). Nevertheless, clinical applicability obstructed by hurdles delivery, patient-specific diversity, pleiotropic signaling. Here, we summarize findings research, including regulatory pathways diagnostic/prognostic biomarkers integrative approaches. We describe delivery systems, such as lipid nanoparticle-based mRNA therapies CRISPR-dCas9-based epigenetic editing that bypass obstacles BBB (blood-brain barrier) enzymatic degradation. recent implementation multiplex panels combining biodynamic indicators with tau amyloid-β signaling markers showcases novel levels specificity both early detection potential monitoring. Humanized preclinical models iPSC-derived neurons organoids point key role neurodeveloping processes, paralleling advances bridging observation environments. Moreover, tools delivering TrkB activators or AI-based dynamic care platforms enable tailored scalable treatments. This review also aims extend framework used understanding BDNF's relevance traditional situating more work detailing actions ischemic tissues gut-brain axis context systemic health. Finally, outline roadmap incorporation BDNF-centered into worldwide healthcare, highlighting ethical issues, equity, interdisciplinary decomposition. heralds new era neuroscience revolutionizing brain health paving way advancement medicine.
Language: Английский
Citations
2
Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1577 - 1577
Published: Oct. 26, 2023
Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, neuronal survival, plasticity, excitability, all of which are disrupted neurological cognitive disorders such as Alzheimer's disease (AD). Extracellular aggregates amyloid-β (Aβ) the form plaques intracellular hyperphosphorylated tau protein have been identified major pathological insults AD brain, along with immune dysfunction, oxidative stress, other toxic stressors. Although aggregated Aβ lead to decreased brain BDNF expression, early losses prior plaque tangle formation may be due stress contribute dysfunction. Physical exercise, on hand, protects structure function, increased mediator exercise-induced enhancements function. Here, we review recent literature mechanisms behind upregulation its effects improving learning memory pathology. Exercise releases into circulation host hormones factors from variety peripheral tissues. Mechanisms induction discussed here osteocalcin, FNDC5/irisin, lactate. The fundamental how exercise impacts cognition not yet fully understood but prerequisite developing new biomarkers therapies delay or prevent decline.
Language: Английский
Citations
22
Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 115994 - 115994
Published: Dec. 9, 2023
Rosmarinic acid (RA), a natural phenolic compound with variety of bioactive properties. However, the antidepressant activity and mechanism RA remain unclear. The aim this study is to investigate effects potential mechanisms on chronic CORT injection induced depression-like behavior in mice. Male C57BL/6 J mice were intraperitoneally injected (10 mg/kg) orally given daily or 20 for 21 consecutive days. In vitro, HT22 cells exposed (200 μM) (12.5, 25 50 LY294002 (a PI3K inhibitor) ANA-12 TrkB treatment. various neurobiological changes cell injury levels target proteins vitro subsequently assessed. Here, treatment decreased expression p-GR/GR, HSP90, FKBP51, SGK-1 hippocampi. Besides, increased average optical density Nissl bodies number dendritic spines CA3 region, enhanced Brdu DCX synaptic transduction DG as well up-regulated both BDNF/TrkB/CREB PI3K/Akt/mTOR signaling. Moreover, reduced structural damage apoptosis cells, differentiation maturation them. More importantly, LY294002, but not ANA-12, reversed effect GR nuclear translocation. Taken together, exerted activities by modulating hippocampal glucocorticoid signaling neurogenesis, which related BDNF/TrkB/PI3K axis regulating translocation, provide evidence application candidate depression.
Language: Английский
Citations
15
Biomedicines, Journal Year: 2023, Volume and Issue: 11(8), P. 2275 - 2275
Published: Aug. 16, 2023
Brain-derived neurotrophic factor (BDNF) is a major neurotrophin whose loss or interruption well established to have numerous intersections with the pathogenesis of progressive neurological disorders. There perhaps no greater example disease resulting from dysregulation BDNF signaling than Huntington’s (HD)—an inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive impairments associated basal ganglia dysfunction ultimate death striatal projection neurons. Investigation collection mechanisms leading in HD highlights this neurotrophin’s importance neuronal viability calls attention opportunities for therapeutic interventions. Using electronic database searches existing forthcoming research, we constructed literature review overarching goal exploring diverse set molecular events that trigger within HD. We highlighted research investigated these preclinical models connected studies those evaluating similar endpoints human subjects. also included special focus on growing body detailing key transcriptomic epigenetic alterations affect abundance Finally, offer critical evaluation proposed neurotrophin-directed therapies assessed clinical trials seeking correct expression individuals.
Language: Английский
Citations
14
European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 971, P. 176525 - 176525
Published: March 30, 2024
Language: Английский
Citations
6
Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(30), P. 5432 - 5447
Published: June 5, 2023
The activity-dependent plasticity of synapses is believed to be the cellular basis learning. These synaptic changes are mediated through coordination local biochemical reactions in and gene transcription nucleus modulate neuronal circuits behavior. protein kinase C (PKC) family isozymes has long been established as critical for plasticity. However, because a lack suitable isozyme-specific tools, role novel subfamily PKC largely unknown. Here, development fluorescence lifetime imaging-fluorescence resonance energy transfer activity sensors, we investigate CA1 pyramidal neurons mice either sex. We find that PKCδ activated downstream TrkB DAG production, spatiotemporal nature its activation depends on stimulation. In response single-spine plasticity, primarily stimulated spine required expression multispine stimulation, long-lasting spreading scales with number spines and, by regulating cAMP response-element binding activity, couples nucleus. Thus, plays dual functional facilitating SIGNIFICANCE STATEMENT Synaptic or ability change strength connections between neurons, underlies learning memory brain health. central this process. understanding how these kinases work mediate limited tools visualize perturb their activity. introduce use new reveal stabilizing spine-to-nucleus signaling regulate transcription. This provides overcome limitations studying function insight into molecular mechanisms
Language: Английский
Citations
13