Brain and Systemic Inflammation in De Novo Parkinson's Disease

Movement Disorders, Год журнала: 2023, Номер 38(5), С. 743 - 754

Опубликована: Фев. 28, 2023

To assess the presence of brain and systemic inflammation in subjects newly diagnosed with Parkinson's disease (PD).Evidence for a pathophysiologic role PD is growing. However, several key gaps remain as to PD, including extent immune activation at early stages, potential effects treatments on whether pro-inflammatory signals are associated clinical features and/or predict more rapid progression.We enrolled de novo (n = 58) age-matched controls 62). Subjects underwent assessments, Movement Disorder Society-United Disease rating scale (MDS-UPDRS). Comprehensive cognitive assessment meeting MDS Level II criteria mild impairment testing was performed. Blood obtained flow cytometry cytokine/chemokine analyses. imaging 18 F-DPA-714, translocator protein 18kd ligand, lumbar puncture if eligible consented.Baseline demographics medical history were comparable between groups. showed significant differences University Pennsylvania Smell Identification Test, Schwab England Activities Daily Living, Scales Outcomes autonomic dysfunction, MDS-UPDRS scores. Cognitive demonstrated composite, executive function, visuospatial domain scores baseline. Positron emission tomography increased F-DPA-714 signal subjects. correlated measures some chemokines.18 central compared controls. Longitudinal follow-up will be important determine predicts decline. © 2023 The Authors. Disorders published by Wiley Periodicals LLC behalf International Parkinson Society.

Язык: Английский

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By what molecular mechanisms do social determinants impact cardiometabolic risk?

Clinical Science, Год журнала: 2023, Номер 137(6), С. 469 - 494

Опубликована: Март 1, 2023

Abstract While it is well known from numerous epidemiologic investigations that social determinants (socioeconomic, environmental, and psychosocial factors exposed to over the life-course) can dramatically impact cardiovascular health, molecular mechanisms by which lead poor cardiometabolic outcomes are not understood. This review comprehensively summarizes a variety of current topics surrounding biological effects adverse (i.e., biology adversity), linking translational laboratory studies with findings. With strong focus on chronic stress, we highlight an array immunological signaling in context health (SDoH). The main covered include biomarkers sympathetic nervous system hypothalamic–pituitary–adrenal axis activation, role inflammation adversity focusing glucocorticoid resistance key inflammatory cytokines linked environmental stressors (PSES). We then further discuss effect SDoH immune cell distribution characterization subset, receptor expression, function. Lastly, describe epigenetic regulation stress response telomere length aging. Ultimately, critical knowledge gaps for future research as strive develop more targeted interventions account improve at-risk, vulnerable populations.

Язык: Английский

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Inflammation, Dopaminergic Brain and Bilirubin

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11478 - 11478

Опубликована: Июль 14, 2023

Dopamine is a well-known neurotransmitter due to its involvement in Parkinson’s disease (PD). not only involved PD but also controls multiple mental and physical activities, such as the pleasure of food, friends loved ones, music, art, mood, cognition, motivation, fear, affective disorders, addiction, attention deficit disorder, depression, schizophrenia. Dopaminergic neurons (DOPAn) are susceptible stressors, inflammation recognized risk for neuronal malfunctioning cell death major neurodegenerative diseases. Less known non-neurodegenerative conditions. Among endogenous defenses, bilirubin, heme metabolite, has been shown possess important anti-inflammatory activity and, most importantly, prevent DOPAn demise an ex vivo model by acting on tumor necrosis factor-alpha (TNFα). This review summarizes evidence linking DOPAn, (when possible, specifically TNFα), bilirubin order understand what known, gaps that need filling, hypotheses strategies preserve dopamine homeostasis with included.

Язык: Английский

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Flexible Electrochemical Dopamine Sensor via Heterojunction Interface Engineerable of Monolayer MoS2 and Electrospun PVA

Surfaces and Interfaces, Год журнала: 2025, Номер unknown, С. 106095 - 106095

Опубликована: Фев. 1, 2025

Язык: Английский

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Progress on Direct Regulation of Systemic Immunity by the Central Nervous System

World Neurosurgery, Год журнала: 2025, Номер 196, С. 123814 - 123814

Опубликована: Март 26, 2025

This article reviews the research progress on direct regulation of immune system by central nervous system. The traditional "neuro-endocrine-immune" network model has confirmed close connection between and However, due to complex mediating role endocrine system, its application in clinical treatment is limited. In recent years, peripheral through provided new methods for neuro-immune related diseases. analyzes changes after injury summarizes effects various stimulation methods, including transcranial magnetic (TMS), electrical (TES), deep brain (DBS), spinal cord stimulation(SCS), vagus nerve stimulation(VNS), system(Figure1). Additionally, it explores future development directions these methods. It proposed that neural techniques exhibit positive reducing inflammation, protecting cells organ functions, improving immunosuppressive states, providing perspectives therapeutic potential immune-related

Язык: Английский

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The antipsychotic drug thiothixene stimulates macrophages to clear pathogenic cells by inducing arginase 1 and continual efferocytosis

Science Signaling, Год журнала: 2025, Номер 18(881)

Опубликована: Апрель 8, 2025

Stimulating efferocytosis, the phagocytic removal of apoptotic cells by macrophages, has been proposed as a method to eliminate dying or dead that accumulate and contribute diseases such cancer, atherosclerosis, infection. Toxicity related off-target clearance healthy tissue led premature termination multiple clinical programs for proefferocytic therapies. To identify potential therapies with established risk profiles, we screened ~3000 US Food Drug Administration (FDA)–approved drugs other well-characterized compounds their capacity stimulate efferocytosis. We found antipsychotic drug thiothixene stimulated efferocytosis lipid-laden mouse human macrophages enhanced continual cells. Consistent thiothixene’s suppressive effects on dopaminergic signaling, dopamine potently inhibited in manner was only partially reversed thiothixene. The prophagocytic depended increased expression gene encoding retinol-binding protein receptor Stra6L, which, turn, promoted production stimulator arginase 1. Our findings demonstrate inhibits thiothixene, generic, FDA-approved use more than 50 years, promising candidate promoting diseased tissue.

Язык: Английский

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Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID‐19 infection

Reviews in Medical Virology, Год журнала: 2024, Номер 34(1)

Опубликована: Янв. 1, 2024

Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. receptors are widely distributed throughout the nervous system cells. Several viruses, human immunodeficiency virus Japanese encephalitis virus, can use dopaminergic to replicate viral neuropathogenesis. In addition, studies suggest that may play role progression pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds angiotensin-converting enzyme on surface neuronal cells, spike protein bind neighbouring cells accelerate its life cycle exacerbate neurological symptoms. recent research has shown dopamine an important regulator immune-neuroendocrine system. Most express other dopamine-related proteins, indicating importance regulation. The increase concentration during SARS-CoV2 infection reduce immunity (innate adaptive) promotes spread, which could lead damage. signalling be affected by COVID -19 cause various symptoms as it interacts with One possible treatment strategy for patients antagonists. To fully understand how protect from we need study pathophysiology

Язык: Английский

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Pramipexole improves depression-like behavior in diabetes mellitus with depression rats by inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing impaired neuroplasticity

Journal of Affective Disorders, Год журнала: 2024, Номер 356, С. 586 - 596

Опубликована: Апрель 22, 2024

Язык: Английский

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Investigating the link between antipsychotic use and post-stroke infections in older people: multi-centre propensity score analysis

Age and Ageing, Год журнала: 2024, Номер 53(6)

Опубликована: Июнь 1, 2024

Abstract Background The risk of stroke increases with age, and although previous reports have suggested that infection may increase antipsychotic use, relevant studies after are scarce. We aimed to investigate whether antipsychotics post-stroke in the acute period. Methods This propensity score matching study included adults diagnosed first-ever between 2011 2020 at five university hospitals. In-hospital exposure was defined as any administration during hospitalisation for stroke. primary outcome first 2 days hospitalisation, secondary presence pneumonia, bacteraemia and/or bacteriuria. Result Among 23,885 patients, 2,773 users (age 71.6 ± 12.4, male 54.6%) non-users 71.2 13.2, were selected matched cohorts. After adjusting score, not associated an increased (odds ratio 0.99, 95% confidence interval 0.87–1.14). Conclusion While our did find conclusive evidence linking medication infection, prescribing these medications should still be approached prudence. Until further research can provide more definitive insights, clinicians carefully weigh potential risks when considering treatment care

Язык: Английский

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Integrating UPLC-MS/MS with in Silico and in Vitro Screening Accelerates the Discovery of Active Compounds in Stephania epigaea

Journal of Pharmaceutical and Biomedical Analysis, Год журнала: 2024, Номер 248, С. 116289 - 116289

Опубликована: Июнь 13, 2024

Язык: Английский

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