Background: Neurovascular coupling (NVC) reflects the relationship between neuronal activity and cerebral blood flow and underpins the interpretation of functional neuroimaging. Disruption of NVC has been linked to aging, vascular pathology, and cognitive decline, and may precede structural brain changes. However, current evidence remains fragmented due to methodological heterogeneity, diverse NVC metrics, and small sample sizes. This systematic review and meta-analysis aim to synthesise available evidence and evaluate NVC as a potential biomarker of cognitive decline. Methods: This protocol follows PRISMA-P guidelines. A systematic search will be conducted in PubMed/MEDLINE, EMBASE, Scopus, Web of Science, and CINAHL. Eligible studies will include adults across the lifespan or individuals with vascular pathology and will report quantitative NVC measures alongside cognitive outcomes. Data extraction will include study characteristics, NVC metrics, cognitive assessments, and relevant physiological factors. A unified statistical approach will be applied to synthesise effect estimates describing associations between NVC, cognition, age, and vascular pathology. Analyses will be stratified by NVC modality, vascular condition, and cognitive domain. Heterogeneity will be assessed using the I² statistic and explored using meta-regression where appropriate. Longitudinal studies will be used to evaluate the predictive value of baseline NVC measures for future cognitive outcomes. Discussion: This study will provide a structured synthesis of current evidence on the role of NVC in cognitive decline across aging and vascular pathology. By integrating findings across diverse methodological approaches, it aims to clarify the strength and consistency of NVC–cognition associations and evaluate the potential of NVC as a sensitive biomarker. The results may inform future research directions and support the development of clinically relevant NVC-based predictive models. Systematic review registration: PROSPERO Registration number: CRD420261351976

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition characterized by repetitive behaviors, impaired sociability, and persistent neuroinflammation. While both epigenetic dysregulation and histaminergic imbalance contribute to ASD pathology, no therapy targets both aspects simultaneously. This study investigated A-366, a selective histone H3K9 methyltransferase G9a inhibitor with additional histamine H3 receptor (H3R) antagonist properties, in BTBR T + tf/J mice (BTBR mice). Sub-chronic administration of A-366 (0.5, 1, or 2 mg/kg, i.p.) dose-dependently reduced repetitive behaviors in marble burying, nestlet shredding, and self-grooming tests, and improved spatial working memory in spontaneous alternation in spontaneous alternation (p < 0.01−0.001 overall). A-366 also restored sociability and social novelty preference (p < 0.001 overall), with the highest dose (2 mg/kg) fully normalizing performance to wild-type levels. At the molecular level, A-366 significantly lowered pro-inflammatory cytokines in cerebellar and hippocampal tissues (p < 0.001 for TNF-α and IL-6; p < 0.05–0.001 for IL-1β). Compared with the reference H3R antagonist Pitolisant, A-366 produced broader behavioral and anti-inflammatory improvements. A-366 also produced broader behavioral and anti-inflammatory improvements and outperformed the dopaminergic–serotonergic modulator, Aripiprazole, at its effective dose. Partial reversal of these effects by coadministration with the selective H3R agonist RAMH indicated that histamine H3R antagonism contributes to its mechanism of action, while G9a inhibition remained unaffected. These findings suggest that A-366 exerts dual therapeutic action by improving ASD-like repetitive and social behaviors and attenuating neuroinflammation, providing a promising scaffold for next-generation multi-target therapeutics.

The metabolic derangements associated with inborn errors of metabolism, metabolic syndrome, and defective autophagy have been linked to neurological manifestations and an increased risk of developing certain neurological diseases or worsening their prognosis. Said metabolic derangements are primarily a consequence of genetic mutations that result in deficiencies of essential cellular components or the accumulation of toxic metabolites that negatively impact neuronal morphology and functionality. Additionally, blood-brain barrier dysfunction, increased quantity and damage of nonneuronal cells, diminished synaptic plasticity, and impediment of protein and neurotransmitter synthesis, among many others, are all neurological implications associated with various metabolic disarrangements. The past few decades have shown substantial efforts in linking various neurological pathologies to genetic variants of metabolic disorders. This review explores the implications of several inborn errors of metabolism, such as phenylketonuria, Wilson's disease, maple syrup urine disease, POLG-related diseases, and lysosomal storage diseases, and the implications of the components of metabolic syndrome in neuronal dysfunction and their link to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and epilepsy. The correlation between defective autophagy, neurodegenerative diseases, and neurodevelopmental diseases is also explored at a molecular level. Congenital disorders of autophagy and their link to neurological pathologies are also discussed. Hence, these correlations provide insight into the underlying biological mechanism of metabolic diseases from a neurological standpoint. This review emphasizes the cruciality of understanding metabolic diseases as important variables in neurological health as well as isolated systemic problems.

IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory deficits. Mounting evidence highlights the role of cholinergic and histaminergic neurotransmissions in the pathophysiology of AD. Hence, developing agents that target multiple neurotransmitter systems may provide improved therapeutic benefits.MethodsThis study investigated the effects of acute systemic administration of E100, a dual-active cholinesterase inhibitor (ChEI) and histamine H3 receptor (H3R) antagonist, on scopolamine (SCO)-induced memory impairment in male C57BL/6 mice. Behavioral assessments, including the Novel Object Recognition Test (NORT), Y-Maze test (YMT), Three-Chamber Test (TCT), Fear Conditioning test (FCT), and Elevated Plus Maze (EPM), were conducted to assess cognitive performance while biochemical analyses assessed apoptotic markers, oxidative stress, neuroinflammation and acetylcholinesterase activity.ResultsSystemic administration of E100 (10 mg/kg, i.p.) significantly improved memory function in SCO-induced amnesia, as evidenced by enhanced short-term memory (STM) (p < 0.001) and long-term memory (LTM) (p < 0.01) performance in the NORT, as well as improved spatial memory in YMT (p < 0.001) and FCT (p < 0.001; for cued fear memory) and (p < 0.001; for contextual fear memory). Additionally, E100 treatment in the TCT, improved social memory (p < 0.001) and alleviated SCO-induced anxiety-related deficits in the EPM (p < 0.001). Moreover, treatment with E100 (10 mg/kg, i.p.) attenuated SCO-induced neuroinflammation by reducing TNF-α and IL-1β levels and mitigated oxidative stress by increasing GSH and SOD while decreasing MDA levels in the hippocampus and cerebellum (p’s < 0.001). E100 also reduced caspase-1 activity (p < 0.001), suggesting its anti-apoptotic effect. Furthermore, E100 attenuated the elevated AChE activity observed in SCO-induced amnesic mice (p < 0.01), providing effects comparable to those of the reference drug Donepezil.DiscussionThese findings provide extensive in vivo evidence of the neuroprotective effects of E100, demonstrating its ability to ameliorate memory deficits, mitigate neuroinflammation and restore oxidative as well as AChE activity balance. By targeting both cholinergic and histaminergic dysfunction in the brain, E100 offers a promising therapeutic strategy for AD and related neurodegenerative disorders. This study highlights the potential role of dual-active ChEIs and H3R antagonists in memory impairment, and addressing multiple neuropathological mechanisms underlying AD.

Diabetes mellitus has been linked to cognitive impairment and Alzheimer's disease (AD). They share common pathologic pathways, including insulin resistance, mitochondrial dysfunction, oxidative stress, and chronic neuroinflammation. These shared mechanisms have prompted interest in repurposing antidiabetic agents as promising therapies for neurodegenerative diseases. Despite this overlap, these drugs face translational challenges, primarily due to their poor penetration across the blood-brain barrier (BBB) and, consequently, poor central nervous system (CNS) bioavailability. Nanoparticle-based drug delivery offers an alternative route to improve targeting of the CNS by increasing the drug stability and augmenting transport across the BBB. Although preclinical evidence showed promising results, the extent to which these findings translate into clinically tangible outcomes remains uncertain. This review critically evaluates the main preclinical studies on nanoparticle-mediated delivery of antidiabetic agents, with particular emphasis on AD and diabetes-associated cognitive impairment, where most available data are concentrated. We also discuss the main brain-targeting strategies, their limitations, and the translational challenges to their clinical application, particularly for conditions beyond AD, where the evidence remains sparse. Addressing these barriers is crucial for the development of nanomedicine-based approaches from bench to bedside. This review provides a critical standpoint on the field and highlights priorities for future research aimed at the effective translation of nanoparticle-enabled therapies for neurodegenerative diseases.

BACKGROUND:Aging is a complex biological process marked by the decline of physiological functions and heightened susceptibility to chronic illnesses, notably cardiometabolic disorders. Ceramides (Cer) are lipid derivatives linked to aging and metabolic diseases. Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), widely used in managing type 2 diabetes, have an unclear impact on aging biomarkers and Cer profiles. OBJECTIVE:This study explored the association between SGLT2i use, plasma Cer levels (CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1), and aging biomarkers-Human Insulin-Like Growth Factor 1 (IGF-1), mammalian target of rapamycin (mTOR), 5-Methylcytosine (5MC), and Human H2AFX (Histone H2AX) in patients with type 2 diabetes mellitus (T2DM). METHODS:In this retrospective study, 95 participants were divided into three groups: patients on SGLT2i (n = 34), patients on non-SGLT2i anti-diabetic treatments (n = 36), and healthy controls (n = 25). Plasma Cer and aging biomarkers were quantified using Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) and ELISA, respectively. Principal component analysis (PCA) assessed group-based clustering, while ANCOVA evaluated group differences with confounder adjustment. RESULTS:SGLT2i-treated patients showed significantly lower CerC16:0, CerC22:0, and CerC24:1 levels (p < 0.01) and decreased 5MC and H2AX (p < 0.05) compared to non-SGLT2i patients. IGF-1 was significantly elevated in the SGLT2i group (p < 0.01), suggesting a possible protective effect on metabolic health. PCA distinguished control from diabetic groups but revealed overlap between SGLT2i and non-SGLT2i groups. CONCLUSION:Beyond glucose control, SGLT2i may improve plasma Cer and aging markers in diabetic patients, supporting their broader therapeutic potential in aging and age-related diseases. Further large-scale studies are warranted to confirm these effects and underlying mechanisms.

Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are neurodevelopmental disorders marked by deficits in communication and social interaction, often accompanied by anxiety, seizures, and intellectual disability. FXS, the most common monogenic cause of ASD, results from silencing of the FMR1 gene and consequent loss of FMRP, a regulator of synaptic protein synthesis. Disruptions in cyclic nucleotide (cAMP and cGMP) signaling underlie both ASD and FXS contributing to impaired neurodevelopment, synaptic plasticity, learning, and memory. Notably, reduced cAMP levels have been observed in platelets, lymphoblastoid cell lines and neural cells from FXS patients as well as Fmr1 KO and dfmr1 Drosophila models, linking FMRP deficiency to impaired cAMP regulation. Phosphodiesterase (PDE) inhibitors, which prevent the breakdown of cAMP and cGMP, have emerged as promising therapeutic candidates due to their ability to modulate neuronal signaling. Several PDE isoforms—including PDE2A, PDE4D, and PDE10A—have been implicated in ASD, and FXS, as they regulate pathways involved in synaptic plasticity, cognition, and social behavior. Preclinical and clinical studies show that PDE inhibition modulates neuroplasticity, neurogenesis, and neuroinflammation, thereby ameliorating autism-related behaviors. BPN14770 (a PDE4 inhibitor) has shown promising efficacy in FXS patients while cilostazol, pentoxifylline, resveratrol, and luteolin have showed improvements in children with ASD. However, challenges such as isoform-specific targeting, optimal therapeutic window, and timing of intervention remain. Collectively, these findings highlight PDE inhibition as a novel therapeutic avenue with the potential to restore cognitive and socio-behavioral functions in ASD and FXS, for which effective targeted treatments remain unavailable.

Introduction:Representing a prominent public health challenge with a surge in cases and no currently available treatment, autism spectrum disorder (ASD) remains a puzzle to researchers. Although the exact pathogenesis of this heterogeneous disorder is yet to be established, it has been reported that neural oxidative stress and neuroinflammation are eminently implicated. With numerous research establishing thymoquinone (TQ) as a potent antioxidant, this study assessed its effectiveness in the context of cognitive and social impairments and neural oxidative stress in the idiopathic autistic model in BTBR mice. Moreover, a novel TQ-loaded nanovesicle drug delivery system was optimized and utilized to enhance the bioavailability of TQ in the central nervous system. Methods:Through a battery of standard behavioral tests, primary parameters such as social behavior, locomotor activity, and anxiety levels were assessed following systemic administration with TQ (10mg/kg, i.p). Biochemical analysis of neural oxidative stress markers in the cerebellum and hippocampus tissue samples obtained from the different treatment groups was also performed. Results:The results indicated significant enhancements in sociability and social novelty preference of assessed BTBR mice treated with TQ-loaded nanovesicles (both p<0.01) as well as free TQ (p<0.05 and p<0.01, respectively). Moreover, BTBR mice treated with TQ-loaded nanovesicles also displayed restored levels of anxiety (p<0.05) and modulated hyperactivity parameters (p<0.05). In addition, and following biochemical assessments, our observations revealed marked alleviation of neural oxidative stress in BTBR mice treated with TQ-loaded nanovesicles, with restored levels of antioxidant proteins, reduced glutathione (p<0.01), and catalase (p<0.01), and diminished levels of the oxidative stress byproduct, malondialdehyde (p<0.01). Discussion:These preclinical observations unraveled compelling findings that reinforced TQ's antioxidant capacity, shedding new light on its potential as an effective therapeutic option for ASD. Thus, and with further experimentation, this study holds the potential to transition into a clinical study.

Autism spectrum disorder (ASD) is a complicated neurodevelopmental syndrome characterized by abnormalities in social communication, lack of interests, and repetitive behaviors. Increasing evidence from recent studies indicates that neuroinflammation and immunological dysregulation play essential roles in the pathogenesis of ASD. This review consolidates current knowledge on two anti-inflammatory cytokines of the IL-1 family, interleukin-38 (IL-38) and interleukin-37 (IL-37), which have recently emerged as essential modulators of neuroimmune mechanisms in ASD, highlighting their emerging roles in ASD pathogenesis and therapeutic potential. Based on a combination of clinical and experimental findings, IL-38 has been reported to exert anti-inflammatory effects by suppressing microglial activation and reducing the release of pro-inflammatory cytokines. Consequently, modulation of IL-38/IL-36R signaling axis appears to represent a crucial mechanism regulating neuroinflammation in brain regions relevant to autism. On the other hand, studies indicate that IL-37 exhibits a consistent upregulation in the brain tissues associated with ASD, functioning via IL-37/IL-18Rα/IL-1R8 pathway, where it inhibits cytokine synthesis, alters microglial polarization, and affects communication along the gut–brain axis. While these findings establish IL-38 and IL-37 as possible biomarkers for ASD diagnosis and treatment targets, these investigations are still emerging. This review establishes the foundation for understanding the growing importance of cytokines and highlights the requirement for further research to clarify their roles and to formulate potential treatment approaches for ASD.

The effects of apigenin, a plant flavonoid, were investigated using the two-electrode voltage-clamp technique on the function of the cloned α7 subunit of the human nicotinic acetylcholine (α7-nACh) receptor expressed in Xenopus oocytes. Currents induced by ACh (100 μM) were reversibly potentiated by apigenin with an EC50 value of 5.4 µM in a voltage-independent manner. In addition, potentiation by apigenin was significantly diminished by increasing ACh concentrations. Furthermore, apigenin (30 µM) did not alter the specific binding of [125I] α-bungarotoxin in oocyte membranes. Moreover, 30 µM apigenin also potentiated [3H] norepinephrine release evoked by nicotine (30 µM) in rat hippocampal slices. Finally, our docking studies carried out for apigenin on nicotinic α7-nACh receptors suggest that apigenin binds to the transmembrane region of the receptor as an allosteric modulator. Taken together, our results indicate that apigenin allosterically potentiates the function of the human α7-nACh receptors expressed in Xenopus oocytes and hippocampal slices.

Accumulation of evidence suggested the involvement of autophagic pathways and their associated AktmTOR (mammalian target of rapamycin) signalling cascade in the pathogenesis of autism spectrum disorder (ASD). Histamine 3 receptors antagonism may be neuroprotective in ASD, as this antagonism modulates autophagy which is reported to be impaired in ASD. Therefore, the effects the novel H3 receptor antagonist E169 (2.5, 5, and 10 mg/kg, i.p.) on short-term memory (STM), long-term memory (LTM), and anxiety level in male Black and Tan BRachyury (BTBR) mice were evaluated using Novel object recognition test (NORT) and open field locomotor (OFT) tests respectively. In NORT, E169 (2.5 mg/kg, i.p.) significantly improved the memory of tested BTBR mice, and the effects of E169 were similar to those of the reference mTOR inhibitor rapamycin, and were reversed following co-administration with the centrally penetrant H3 receptor agonist (R)-α-methylhistamine (RAMH). Furthermore, E169 enhanced the BTBR memory by inhibiting H3 receptors and regulating the extent of disruption in the expression of cerebellar Akt, mTOR, and LC-3 proteins of treated mice. Moreover, E169 (2.5 mg/kg, i.p.) restored the disturbed anxiety levels and hyperactivity observed in OFT. In summary, the findings indicate that H3 receptor antagonists like E169 could play a role in simultaneously regulating disrupted brain neurotransmitters and the dysregulated cerebellar Akt-mTOR signaling pathway associated with autophagy in neurological diseases. Therefore, activation of cerebellar autophagy represented by H3 receptor antagonist E169 may serve as an effective pharmacological therapeutic target for the ASD-like behavioral phenotypes and may add new therapeutic management strategy for the multifactorial disorder ASD.

Neuropsychiatric disorders present a multifaceted challenge, characterized by cognitive, social, and motor impairments with manifold underlying mechanisms. Recent attention has turned to epigenetic mechanisms, particularly histone lysine methyltransferases (HKMTs), such as G9a, in understanding fundamental pathogenesis. This review provides a concise overview of the structural and functional features of G9a and its involvement in neuropsychiatric disorders, including neurodevelopmental disorders (NDDs) like autism spectrum disorders (ASD) and Prader-Willi syndrome (PWS), schizophrenia (SZ), epilepsy, anxiety, depression, and Alzheimer's disease (AD). Furthermore, it highlights the biochemical mechanisms of G9a-mediated histone methylations and explores pharmacological interventions targeting G9a for potential therapeutic avenues. This current knowledge underlines G9a's significance as a therapeutic target and sets the stage for future investigations into its role in neuropsychiatric disorders.

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social interaction difficulties, repetitive behaviors, and immune dysregulation with elevated pro-inflammatory markers. Autophagic deficiency also contributes to social behavior deficits in ASD. Histamine H3 receptor (H3R) antagonism is a potential treatment strategy for brain disorders with features overlapping ASD, such as schizophrenia and Alzheimer’s disease. Methods: This study investigated the effects of sub-chronic systemic treatment with the H3R antagonist E159 on social deficits, repetitive behaviors, neuroinflammation, and autophagic disruption in male BTBR mice. Results: E159 (2.5, 5, and 10 mg/kg, i.p.) improved stereotypic repetitive behavior by reducing self-grooming time and enhancing spontaneous alternation in addition to attenuating social deficits. It also decreased pro-inflammatory cytokines in the cerebellum and hippocampus of treated BTBR mice. In BTBR mice, reduced expression of autophagy-related proteins LC3A/B and Beclin 1 was observed, which was elevated following treatment with E159, attenuating the disruption in autophagy. The co-administration with the H3R agonist MHA (10 mg/kg, i.p.) reversed these effects, highlighting the role of histaminergic neurotransmission in observed behavioral improvements. Conclusions: These preliminary findings suggest the therapeutic potential of H3R antagonists in targeting neuroinflammation and autophagic disruption to improve ASD-like behaviors.

Postmortem studies have revealed that brains of individuals with autism spectrum disorder (ASD) exhibit abnormalities in various components of the cholinergic system including cholinergic receptors, projections, and nuclei. Deletions in the 15q13.3 region which encompasses CHRNA7, the gene that encodes the α7-nACh receptor, have been linked to various neurodevelopmental disorders, including ASD. In addition, the involvement of α7-nACh receptors in biological phenomena known to play a role in the pathophysiology of ASD such as cognitive functions, learning, memory, neuroinflammation, and oxidative stress, as well as the excitation-inhibition balance in neuronal circuits and maternal immune activation have been reported in previous studies. Furthermore, evolving preclinical and clinical literature supports the potential therapeutic benefits of using selectively acting cholinergic compounds, particularly those targeting the α7-nACh receptor subtype, in the treatment of ASD. This study reviews the previous literature on the involvement of nACh receptors in the pathophysiology of ASD and focuses on the α7-nACh receptor as a potential therapeutic target.

Introduction: Brain histamine is considered an endogenous anticonvulsant and histamine H1 receptor. H1R antagonists have, in earlier studies, been found to induce convulsions. Moreover, research during the last two decades has provided more information concerning the anticonvulsant activities of histamine H3R (H3R) antagonists investigated in a variety of animal epilepsy models.Methods: Therefore, the in vivo anticonvulsant effect of the H3R antagonist DL76, with proven high in vitro affinity, in vitro selectivity profile, and high in vivo antagonist potency in mice against maximal electroshock (MES)-induced seizures in mice, was assessed. Valproic acid (VPA) was used as a reference antiepileptic drug (AED). In addition, DL76 was tested for its reproductive and fetal toxicity in the same animal species.Results and discussion: Our observations showed that acute systemic administration (intraperitoneal; i.p.) of DL76 (7.5 mg/kg, 15 mg/kg, 30 mg/kg, and 60 mg/kg, i.p.) provided significant and dose-dependent protection against MES-induced seizures in female and male mice. Moreover, the DL76-provided protective effects were comparable to those offered by the VPA and were reversed when animals were co-administered the CNS-penetrant selective H3R agonist R-(α)-methylhistamine (RAM, 10 mg/kg, i.p.). Furthermore, the administration of single (7.5 mg/kg, 15 mg/kg, 30 mg/kg, or 60 mg/kg, i.p.) or multiple doses (3 × 15 mg/kg, i.p.) of H3R antagonist DL76 on gestation days (GD) 8 or 13 failed to affect the maternal body weight of mice when compared with the control mice group. No significant alterations were detected in the average number of implantations and resorptions between the control and DL76-treated groups at the early stages of gestation and the organogenesis period. In addition, no significant differences in the occurrence of skeletal abnormalities, urogenital abnormalities, exencephaly, exomphalos, facial clefts, and caudal malformations were observed. The only significant abnormalities witnessed in the treated groups of mice were in the length of long bones and body length. In conclusion, the novel H3R antagonist DL76 protected test animals against MES-induced seizures and had a low incidence of reproductive and fetal malformation with decreased long bone lengths in vivo, signifying the potential therapeutic value of H3R antagonist DL76 for future preclinical as well as clinical development for use in the management of epilepsy.

Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota–gut–brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut–brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer’s disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer’s neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson–Konovalov disease (WD), multisystem atrophy (MSA), Huntington’s chorea (HC), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut–brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.

Abstract Background Addressing knowledge and concerns related to corticosteroid is essential to enhance patient care, promote optimal utilization, and minimize their potential side effects. Methods A cross-sectional study was conducted to assess knowledge and attitudes regarding corticosteroid use among healthcare providers (HCPs) in the United Arab Emirates using a validated questionnaire. Knowledge, attitudes, and fear items were described as frequency and percentages. Then, a total score was calculated; multilinear regression was used to see the effect of demographics on these scores. Results Among 129 HCPs, 100 had previously prescribed corticosteroids (77.5%), with intranasal spray being the most dispensed dosage form (89.0%). Respiratory diseases were the most reported indication for corticosteroid dispensing (93.0%). HCPs preferred corticosteroids for their ability to quickly relief of patients' symptoms (67.0%). About 60.0% identified increased appetite as a patient-reported side effect. The assessment of the HCPs' knowledge showed a median score of 10 out of 11 (IQR = 9–11). The median fear score was six out of 10 (IQR = 4–10), but they were significantly and conversely related to each other. Conclusion This study revealed that while HCPs in the UAE possess substantial knowledge regarding corticosteroid use, their concerns, particularly around side effects, indicate a need for further education. Addressing these concerns through targeted educational programs could enhance the safe and effective utilization of corticosteroids, ultimately improving patient care outcomes.