Alzheimer’s disease (AD) is a gradually worsening neurodegenerative disorder marked by memory impairment, poor judgment, difficulty completing tasks, changes in Behaviour, hallucinations, and delusions. The underlying mechanism of AD featured extracellular aggregation of the Aβ plaques, intracellular deposition of tau protein, accumulation of neurofibrillary tangles (NFTs), and synaptic dysfunction. In the central nervous system (CNS), purines, namely adenosine triphosphate (ATP) and its metabolites like adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine, function extracellularly. The P2X7 receptor (P2X7R) is a trimeric, ion-gated channel regulated by ATP, found in neurons, astrocytes, oligodendrocytes, and microglia. Several in-vivo and in-vitro studies have implied the importance of P2X7R in the brain pathology of AD. In AD, activation of P2X7R results in mechanisms contributing to its pathophysiology, such as neuroinflammation, accumulation of amyloid‑β, amyloid precursor protein processing (APP), oxidative stress, and synaptic dysfunction. Furthermore, this process leads to the production and release of chemokines and triggers the inflammasome pathway, particularly NLRP3, which modulates the inflammatory response and manages amyloid‑β accumulation by controlling both the NLRP3 inflammasome pathway and the expression of several chemokines. Thus, pharmacological inhibition or knockdown of P2X7R leads to improvement in symptoms of various AD mouse models. This review focuses on the functions and role of P2X7R in the mechanisms of AD pathophysiology, including neuroinflammation, oxidative stress, accumulation of amyloid‑β, synaptic dysfunction, and APP processing, and acts as an emerging target in AD.
Aim To comprehensively characterise the structural, epigenetic, and functional genomic landscape of chromosome 11 and to elucidate its role in the pathogenesis of imprinting disorders, malignancies, neuropsychiatric conditions, metabolic dysregulation Objectives 1. To investigate imprinting control mechanisms at chromosome 11p15 and their contribution to disorders such as Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS). 2. To evaluate oncogenic amplification events at 11q13, particularly involving CCND1, and their role in tumorigenesis via cell-cycle dysregulation. 3. To analyze linkage disequilibrium-resolved variants in neuropsychiatric loci (DRD2, NCAM1, GRIK4) and their impact on neurotransmission pathways. 4. To examine coding and epigenetic alterations in metabolic genes (INS, KCNQ1, IGF2/H19) associated with diabetes and congenital hyperinsulinism. Results Integrative genomic analyses demonstrated that chromosome 11 exhibits extensive heterogeneity, encompassing imprinting domains, oncogenic loci, metabolic regulators, and neuropsychiatric susceptibility regions. Aberrant methylation at 11p15 underlies imprinting disorders such as BWS and SRS. Amplification of 11q13, particularly involving CCND1, promotes tumorigenesis via G1–S cell-cycle progression. Functional variants in neuropsychiatric genes disrupt dopaminergic and glutamatergic signaling, influencing synaptic plasticity. Metabolic gene perturbations impair β-cell function, contributing to diabetes and hyperinsulinism. Long-read sequencing with haplotype phasing enhances the detection of pathogenic variants in the HBB locus, improving diagnostic accuracy for β-thalassemia and sickle-cell disease.
Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive motor and non-motor symptoms, dopaminergic neuronal loss, and pathological α-synuclein aggregation (Kalia & Lang, 2015; Poewe et al., 2017).Despite substantial advances in understanding PD pathogenesis, the identification of reliable biomarkers for early diagnosis, prognostic stratification, and therapeutic targeting remains limited (Tolosa et al., 2021; Blauwendraat et al., 2020).G-protein-coupled receptors (GPCRs) play central roles in neurotransmission, immune regulation, and neuroinflammatory signaling, positioning them as promising candidates for biomarker discovery and therapeutic intervention in neurodegenerative diseases (Pierce et al., 2002; Insel et al., 2019).In this study, we performed an integrative transcriptomic and systems-level analysis of the publicly available GSE49036 dataset to identify GPCR-related biomarkers associated with PD (GEO Accession: GSE49036; Barrett et al., 2013).Differential expression analysis, functional enrichment, and protein–protein interaction network construction identified NTSR1 and GPR161 as key hub genes within GPCR-associated regulatory modules (Szklarczyk et al., 2019; Yu et al., 2012).Predictive nomogram modeling demonstrated the diagnostic potential of these biomarkers, while gene set enrichment analysis and consensus clustering revealed associations with DNA replication stress, GPCR signaling cascades, immune regulation, and distinct molecular PD subtypes (Subramanian et al., 2005; Wilkerson & Hayes, 2010).Single-sample gene set enrichment analysis (ssGSEA) further indicated that biomarker expression correlated with immune cell infiltration patterns, including enrichment of innate immune populations and immunosuppressive phenotypes (Hänzelmann et al., 2013; Tansey & Romero-Ramos, 2019).Integrated regulatory network analyses identified interacting miRNAs, proteins, and candidate therapeutics targeting NTSR1- and GPR161-associated pathways, suggesting potential translational and drug-repurposing applications (Ritchie et al., 2015; Karuppagounder et al., 2021).Finally, RT-qPCR validation in independent clinical samples confirmed the overexpression of NTSR1 and GPR161, supporting their biological relevance and robustness as GPCR-based biomarkers in PD (Bustin et al., 2009).Collectively, this study provides a systematic framework for GPCR-driven biomarker discovery in Parkinson’s disease, offering novel insights into disease mechanisms, neuroimmune interactions, and precision medicine strategies (Bloem et al., 2021; Insel et al., 2019).
Diabetes mellitus, a chronic metabolic disorder, requires lifelong insulin therapy, typically administered via subcutaneous injections. Despite its efficacy, the invasive nature of injections and patient non-compliance highlight the need for alternative non-invasive delivery systems. This study proposes the development of a novel oral insulin delivery system using PEGylated liposomal nanocarriers functionalized with sodium taurocholate, aiming to enhance insulin bioavailability, stability, and therapeutic efficacy. PEGylation serves to protect insulin from enzymatic degradation in the gastrointestinal tract, while sodium taurocholate facilitates improved absorption by modulating intestinal permeability. The prepared formulation was characterized for size, morphology, and encapsulation efficiency, followed by in vitro studies evaluating its protective ability against enzymatic degradation and absorption enhancement. In vivo pharmacokinetic studies in diabetic animal models assessed the bioavailability, therapeutic efficacy, and controlled release of the oral insulin formulation. The results of this study are expected to demonstrate that the PEGylated liposomal insulin formulation offers a promising, non-invasive alternative to subcutaneous injections, improving patient compliance and optimizing insulin therapy.
