Current Signal Transduction Therapy - Volume 20, Issue 2, 2025

Parkinson’s Disease (PD) is a common neurodegenerative disease, characterized by motor deficit. Diabetes Mellitus (DM) is a metabolic condition characterized by high glucose levels in the blood. The prevalence of chronic disorders like PD has significantly risen in recent decades. Emerging research has increasingly linked PD with Type 2 Diabetes Mellitus (T2DM) in recent years. Apart from the β-cells of the pancreas, insulin is secreted by the choroid plexus in the human brain which is essential for neuroprotection which regulates neurogenesis, oxidative stress, synaptic plasticity, neuronal survival, and neuro-inflammation. The abnormalities in the insulin signaling pathway may be responsible for neurodegeneration via insulin dysregulation, from the aggregation of α-synuclein, neuroinflammation, mitochondrial dysfunction, and altered synaptic plasticity. DM or Insulin resistance is considered a risk factor for the development of PD. Due to the lack of treatment options for PD, consistent research is going on to find a potential drug as a treatment option for PD, and due to its molecular links, the antidiabetic drugs are considered as potential candidates for PD. This review will discuss the potential cellular mechanisms shared between T2DM and PD as well as the role of antidiabetics in this disease and clinical manifestations such as its severity and prognosis.

Pattern Recognition Receptors (PRRs), particularly Toll-like Receptors (TLRs), are pivotal in the innate immune system for recognizing Pathogen-associated Molecular Patterns (PAMPs) and initiating inflammatory responses. TLRs, characterized by their transmembrane structure, Leucine-rich Repeat (LRR) ectodomain, and Toll/Interleukin-1 Receptor (TIR) domains, detect a diverse range of microbial and endogenous ligands through MyD88- and TRIF-dependent pathways. This engagement activates downstream signaling cascades involving key mediators such as Nuclear Factor Kappa B (NF-κB), Mitogen-activated Protein (MAP) kinases, and Interferon Regulatory Factors (IRFs), which orchestrate pro-inflammatory cytokine production and immune responses. TLRs are not only implicated in various pathologies like multiple sclerosis, rheumatoid arthritis, and atherosclerosis but also show potential in diagnosing and preventing infectious diseases like dengue fever and periodontal disease. Recent advancements reveal their dual role as both agonists and antagonists in enhancing vaccine responses and developing novel cancer immunotherapies. This review provides a comprehensive synthesis of recent research and patents on TLRs, emphasizing novel therapeutic strategies and targeted delivery systems for biomedical applications. The future scope of TLR research is explored, with a focus on how TLR-targeted therapies could transform the management of inflammatory and immune-mediated disorders.

Novo Nordisk has innovated a subcutaneous formulation of semaglutide, branded as Ozempic, which functions as a modified human glucagon-like peptide-1 (GLP-1) analogue. This formulation is tailored to address the treatment needs of individuals diagnosed with type 2 diabetes mellitus (T2DM). By providing a modified version of the naturally occurring hormone GLP-1, Ozempic offers a therapeutic approach that targets glucose metabolism and helps regulate blood sugar levels in patients with this condition. It has been endorsed as a secondary treatment for improving glycemic control in T2DM, and it is currently being investigated for its potential in combating obesity. Studies have demonstrated that semaglutide is safe for use in both adult and elderly patients with renal or hepatic conditions, requiring no adjustment in dosage. Semaglutide is a GLP-1RA drug that is used to reduce chronic obesity and the dosage used is 2.4 mg for the patients. The study highlighted the effects of the semaglutide drug on patients with obesity and T2DM. The drug exerts several adverse side effects on co-morbid patients with T2DM and obesity. Semaglutide targets the specific area of the brain (GLP-1 receptors), which is beneficial for the regulation of the appetite and helps to manage weight. Semaglutide imitates the function of incretin. The fluctuation of the blood sugar level can be controlled with semaglutide. The long-term health complications related to diabetes can be decreased with semaglutide. This study highlights the safety concerns and risk factors associated with semaglutide.