Unveiling the Molecular Interactions Between Human Transferrin and Limonene: Natural Compounds in Alzheimer’s Disease Therapeutics

Abstract

Background: Neurodegeneration is a term describing an irreversible process of neuronal damage. In recent decades, research efforts have been directed towards deepening our knowledge of numerous neurodegenerative disorders, with a particular focus on conditions such as Alzheimer’s disease (AD). Human transferrin (htf) is a key player in maintaining iron homeostasis within brain cells. Any disturbance in this equilibrium gives rise to the emergence of neurodegenerative diseases and associated pathologies, particularly AD. Limonene, a natural compound found in citrus fruits and various plants, has shown potential neuroprotective properties. Objective: In this study, our goal was to unravel the binding of limonene with htf, with the intention of comprehending the interaction mechanism of limonene with htf. Methods: Binding was scrutinized using fluorescence quenching and UV-Vis spectroscopic analyses. The binding mechanism of limonene was further investigated at the atomic level through molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies. Results: Molecular docking uncovered that limonene interacted extensively with the deep cavity located within the htf binding pocket. MD results indicated that binding of limonene to htf did not induce substantial structural alterations, ultimately forming stable complex. The findings from fluorescence binding indicated a pronounced interaction between limonene and htf, limonene binds to htf with a binding constant (K) of 0.1×105 M–1. UV spectroscopy also advocated stable htf-limonene complex formation. Conclusions: The study deciphered the binding mechanism of limonene with htf, providing a platform to use limonene in AD therapeutics in context of iron homeostasis.

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

“…Plant-derived compounds, specifically flavonoids like limonene, curcumin, naringin, resveratrol, crocin, and naringenin, have gained significant attention for AD treatment during the past decades due to their promising neuroprotective effects via binding to toxicity, ansferrin, downregulating TNF-α, nitric oxide, and oxidative stress, reducing Aβ protein generation and ROS clearance, hindering proinflammatory cytokines’ production, plus mitochondrial toxicity and cholinergic dysfunction reduction. − In this context, multiple studies have investigated the therapeutic potency of SA in AD models. SA administration in AD in vivo models, induced by Aβ (1–42), AlCl 3 , and streptozotocin, demonstrated neuronal cell death reduction, glial cell activation, iNOS expression enhancement, and increased antioxidant enzyme levels leading to memory loss prevention and MAO-A and MAO-B blockade, in addition to an appropriate response to chemical and pathological changes in induced memory and learning impairment. − In scopolamine-induced AD models, Lee et al demonstrated SA’s potency to ameliorate both long- and short-term spatial memory deficits as well as avoid memory loss through upregulation of hippocampus synaptic activity and the stimulation of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) expression.…”