Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Immune-Driven Mechanisms in Idiopathic Intracranial Hypertension: A Critical Synthesis(Walter de Gruyter GmbH, 2026) Tuzun, Erdem; Yetimler, BerrakIdiopathic intracranial hypertension (IIH) is increasingly recognised as a complex disorder characterized by elevated intracranial pressure (ICP), with evidence suggesting contributions from dysregulated cerebrospinal fluid (CSF) dynamics as well as metabolic, endocrine, and neurovascular mechanisms. IIH predominantly affects women of reproductive age who are living with obesity. Clinically, IIH may be asymptomatic or present with severe headaches, visual disturbances, and papilledema, with a risk of visual impairment in some untreated or refractory cases. Although the etiopathogenesis of IIH remains unclear, emerging evidence from metabolic and immunological studies suggests that immune-mediated mechanisms may contribute to disease pathophysiology. In this review, we synthesize current literature on the potential contribution of the immune system to IIH, integrating findings across obesity-associated inflammation, circulating cytokine profiles, comorbid inflammatory and autoimmune conditions, and markers of neuroglial stress and injury. We summarize converging data suggesting that IIH may, at least in part, be influenced by a pro-inflammatory milieu that affects CSF dynamics. While available studies highlight intriguing immunological signals, the underlying mechanistic pathways remain poorly resolved. Larger, longitudinal, and mechanistically grounded investigations are needed to clarify causality, identify relevant immune subtypes, and determine whether immune modulation may offer therapeutic opportunities in IIH.Article Citation - WoS: 5Citation - Scopus: 5Targeting Cholinergic Dysfunction and Neuroinflammation through Rationally Designed Thieno[3,2-d]Pyrimidine Hybrids(Academic Press Inc Elsevier Science, 2026-07) Acar, Ozden Ozgun; Acar, Busra; Senol, Halil; Tokali, Feyzi Sinan; Sen, Alaattin; Demir, Yeliz; Cakir, FurkanNeurodegenerative diseases involve the convergence of cholinergic dysfunction, neuronal loss, and sustained neuroinflammatory responses, necessitating the development of multifunctional therapeutic agents. In this study, a series of novel thieno[3,2-d]pyrimidine-phenolic Mannich base hybrids were rationally designed, synthesized, and evaluated as dual cholinesterase inhibitors with neuroprotective and anti-neuroinflammatory potential. The synthesized compounds exhibited potent inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with inhibition constants in the low nanomolar range. Among them, compounds 5 and 9 emerged as the most active derivatives, displaying Ki values of 8.79 and 14.11 nM for AChE and 7.04 and 11.75 nM for BChE, surpassing the reference inhibitors tacrine and donepezil. Molecular docking and molecular dynamics simulations supported the experimental findings, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations further confirmed their superior binding affinities compared with donepezil. Cytotoxicity profiling in SH-SY5Y neuronal cells and RAW 264.7 and THP-1 immune cells identified a narrow sub-cytotoxic concentration window (EC05-EC10 = 1.2-2.1 mu M), ensuring biological effects independent of nonspecific cell damage. Within this range, both compounds exerted pronounced antineuroinflammatory activity. Notably, compound 9 significantly downregulated pro-inflammatory mediators, reducing IL-1 beta, IL-6, and NF-kappa B1 gene expression by up to 2.78-, 3.37-, and 4.84-fold, respectively. Consistently, it suppressed nitric oxide production in LPS-stimulated macrophages to levels comparable with ascorbic acid and markedly decreased Iba1 expression in activated THP-1 cells. This integrated enzymatic, computational, and cellular investigation identifies compounds 5 and 9 as promising multifunctional lead combining dual cholinesterase inhibition with robust anti-neuroinflammatory activity. The results provide a strong foundation for future in vivo studies and further optimization toward disease-modifying agents for neurodegenerative disorders.