Developments in Neurodegenerative Disorders: Highly Cited Articles Published in Brain Sciences in 2023–2024

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 345 - 345

Published: March 27, 2025

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS), pose a significant growing health concern, particularly in developed countries [...]

Language: Английский

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TREM 2 in Parkinson’s Disease: A Promising Candidate Gene for Disease Susceptibility and Progression

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 379 - 379

Published: April 5, 2025

Background/Objectives: The activation of microglia and the activity innate immunity have recently been recognized as part Parkinson’s Disease (PD) pathophysiology. Triggering receptor expressed on myeloid cells 2 (TREM2) is a gene with neuroprotective roles. Its variations are associated microglial-associated neurodegeneration. objective present review to investigate current evidence role TREM2 in PD Methods: A comprehensive search was performed using PubMed, Medline, Web Science, looking for English papers investigating PD, or more general, genetic profile microglia. Results: Thirty-one were considered relevant. Preclinical studies models showed some contradictory results, even if loss function generally microglial α-synuclein-induced inflammatory processes. patients should be taken caution. increase soluble extracellular segment (sTREM2) cerebrospinal fluid seems increased risk cognitive decline. Conclusions: There increasing that may an important pathophysiology demonstrated by preclinical clinical studies. Further investigations needed confirm this lead way future targeted therapies different neurodegenerative disorders.

Language: Английский

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Different Levels of Therapeutic Strategies to Recover the Microbiome to Prevent/Delay Acute Lymphoblastic Leukemia (ALL) or Arrest Its Progression in Children

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3928 - 3928

Published: March 31, 2024

Changes in the components, variety, metabolism, and products of microbiomes, particularly gut microbiome (GM), have been revealed to be closely associated with onset progression numerous human illnesses, including hematological neoplasms. Among latter pathologies, there is acute lymphoblastic leukemia (ALL), most widespread malignant neoplasm pediatric subjects. Accordingly, ALL cases present a typical dysfunctional GM during all its clinical stages resulting inflammation, which contributes progression, altered response therapy, possible relapses. Children characteristic variations composition, functions, such alterations may influence predict complications prognosis after chemotherapy treatment or stem cell hematopoietic transplants. In addition, growing evidence also reports ability formation, growth, roles newborn's system through process developmental programming fetal life as well susceptibility onco-hematological namely ALL. Here, we suggest some therapeutic strategies that can applied at two levels intervention recover consequently prevent/delay arrest progression.

Language: Английский

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Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

Published: Nov. 27, 2023

With the term neuroinflammation has defined typical inflammatory response of brain closely related to onset many neurological diseases. Neuroinflammation is well known, but its mechanisms and pathways are not entirely comprehended. Currently, some progress been achieved through efforts research. Consequently, new cellular molecular mecha-nisms, diverse from conventional ones, emerging. In listing those that will be sub-ject our description discussion, essential important role peripheral infiltrated monocytes clonotypic cells, alterations in gut/brain axis, dysregulation apelinergic sys-tem, as changes endothelial glycocalyx blood-brain barrier, variation expres-sion genes levels encoding molecules by microRNAs (miRNAs), or other epige-netic factors distinctive transcriptional factors, autophagy, ferroptosis, sex differences modifications circadian cycle. Such mentioned can add significant pieces understanding complex etiological puzzle neuroinflammation. addi-tion, they could represent biomarkers targets neurodegenerative diseases, increase old populations.

Language: Английский

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Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Abstract Background Blood-based biomarkers are gaining grounds for Alzheimer’s disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods multi-analyte assessments and markers neuroinflammation, vascular, synaptic dysfunction. Here, we evaluated a novel biomarker platform, NULISAseq CNS panel, multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ∼120 analytes, including classical AD proteins defining various hallmarks. Methods The panel was applied 176 plasma samples from MYHAT-NI cohort cognitively normal participants an economically underserved region in Western Pennsylvania. Classical biomarkers, p-tau181, p-tau217, p-tau231, GFAP, NEFL, Aβ40, Aβ42, were also measured using Single Molecule Array (Simoa). Amyloid pathology, tau neurodegeneration with [11C] PiB PET, [18F]AV-1451 MRI, respectively. Linear mixed models used examine cross-sectional Wilcoxon rank sum tests longitudinal associations between NULISA pathologies. Spearman correlations compare Simoa. Results concurrently 116 good technical performance, correlation Simoa measures. Cross-sectionally, p-tau217 top hit identify Aβ age, sex, APOE genotype-adjusted AUC 0.930 (95%CI: 0.878-0.983). Fourteen significantly decreased Aβ-PET+ participants, TIMP3, which regulates brain production, neurotrophic factor BDNF, energy metabolism marker MDH1, several cytokines. Longitudinally, FGF2, IL4, IL9 exhibited PET-dependent yearly increases participants. Markers changes included microglial activation CHIT1, reactive astrogliosis CHI3L1, protein NPTX1, cerebrovascular PGF, PDGFRB, VEFGA; all previously linked but only reliably cerebrospinal fluid. SQSTM1, autophagosome cargo protein, significant association status after adjusting ε4 genotype. Conclusions Together, our results demonstrate feasibility potential immunoassay-based multiplexing provide comprehensive view AD-associated proteomic changes. Further validation identified inflammation, synaptic, vascular will important establishing state asymptomatic AD.

Language: Английский

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Phytosome-Encapsulated 6-Gingerol- and 6-Shogaol-Enriched Extracts from Zingiber officinale Roscoe Protect against Oxidative Stress-Induced Neurotoxicity

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 6046 - 6046

Published: Dec. 22, 2024

The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates neuroprotective potential phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Zingiber officinale Roscoe (6GS), bioactive compounds renowned their antioxidant anti-inflammatory properties. novel phytosome encapsulation technology employed enhances bioavailability stability these compounds, offering superior therapeutic compared conventional formulations. Additionally, investigates role phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-signaling pathway, a key mediator effects 6GS. Neurotoxicity was induced in SH-SY5Y cells (a human neuroblastoma line) using 200 μM hydrogen peroxide (H2O2), following pretreatment with 6GS at concentrations 15.625 31.25 μg/mL. Cell viability assessed via MTT assay alongside evaluations reactive oxygen species (ROS), enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), oxidative stress markers (malondialdehyde [MDA]), molecular mechanisms involving PI3K/Akt apoptotic factors (B-cell lymphoma-2 [Bcl-2] caspase-3), inflammatory (tumor necrosis factor-alpha [TNF-α]). results demonstrated that significantly improved viability, reduced ROS, MDA, TNF-α, caspase-3 levels, enhanced activities. Furthermore, treatment upregulated PI3K, Akt, Bcl-2 expression while suppressing activation. Activation pathway by led phosphorylated Akt-mediated upregulation Bcl-2, promoting survival attenuating inflammation. Moreover, inhibited ROS generation, further mitigating neurotoxicity. These findings suggest 6GS, which through activation exhibits significant Incorporating into functional foods or dietary supplements could offer promising strategy addressing neuroinflammation associated diseases.

Language: Английский

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Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Abstract The risk of developing Parkinson’s disease (PD) is elevated in people with type 2 diabetes, but the precise molecular pathways underlying this connection are still unclear. One hypothesis that glycation, a non-enzymatic family reactions between glycating agents, such as reducing sugars or reactive dicarbonyls, and specific amino acids, lysines arginines, may alter proteostasis trigger pathological alterations. Glycation alpha-synuclein (aSyn), central player PD pathology, causes profound changes aggregation process aSyn. Methylglyoxal (MGO), strong agent, induces formation inclusions enriched phosphorylated aSyn on serine 129 (pS129). In addition, we found neuroinflammatory responses enhanced by MGO-mediated glycation. Using novel polyclonal antibodies developed towards MGO-glycated residues, confirmed occurrence glycated both vitro well animal human brain tissue. total, our findings shed light into interplay PD, potentially paving way for development therapeutic strategies targeting these intertwined conditions.

Language: Английский

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Intraperitoneal Injection of the Porphyromonas gingivalis Outer Membrane Vesicle (OMV) Stimulated Expressions of Neuroinflammatory Markers and Histopathological Changes in the Brains of Adult Zebrafish

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11025 - 11025

Published: Oct. 14, 2024

Porphyromonas gingivalis is the major pathogenic bacteria found in subgingival plaque of patients with periodontitis, which leads to neuroinflammation. The destroy periodontal tissue through virulence factors, are retained bacteria's outer membrane vesicles (OMV). This study aimed determine real-time effect an intraperitoneal injection P. OMV on production and expression inflammatory markers histopathological changes adult zebrafishes' central nervous systems (CNS). Following LD50 (21 µg OMV), zebrafish were injected intraperitoneally 18 OMVs, control group normal saline at seven different time points. Brains experimental dissected desired points for colorimetric assays, ELISA, histology. discovered that nitric oxide PGE2 significantly increased 45 min, while IL-1β IL-6 expressed subsequent 12 h 24 points, respectively. Histopathological such as blood coagulation, astrocytosis, edema, spongiosis, necrosis observed between 6hour two apoptotic enzymes, caspases 3 9, not any point. In summary, OMV-induced neuroinflammatory responses time-point dependent. will enrich our understanding mechanism OMVs neuroinflammation a model, most especially timing mediators relation observable brain tissues.

Language: Английский

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