Catecholamine Neurotransmitters Research Articles

Electrochemical evaluation of magnetic reduced graphene oxide nanosheet‐modified glassy carbon electrode on dopamine electrochemical sensor for Parkinson's diagnostic application

AbstractBackgroundDopamine is an important catecholamine neurotransmitter that plays a critical function as a chemical messenger that aids in the signal transmission in the brain and other important places. Dopamine is known to play an important role in several neurological diseases such as schizophrenia and Parkinson's disease in which a key factor in the development of Parkinson's disease is abnormally lower levels of dopamine compared to normal levels. However, these methods are expensive, requires manual labor and resources, and demands large number of reagents and chemicals. Therefore, it is essential to develop dopamine detection methods that are less costly, more stable, and easier to perform.ObjectiveTo develop a magnetic reduced graphene oxide (MRGO) nanosheet‐modified glassy carbon electrode (GCE) for the electrochemical detection of dopamine.MethodsMagnetic reduced graphene oxide (MRGO) nanosheet were prepared by the in situ coprecipitation of Fe3+ and Fe2+ in the GO solution. To prepare the MRGO nanosheet ink, 38 mg of MRGO nanosheet was mixed with 2 mg of acetylene black and 80 μL of Nafion solution (5%). The mixture was then mixed with 210 μL of deionized water and 210 μL of 2‐propanol and subjected to ultrasonication for 120 min using a sonicator to obtain a homogenous MRGO nanosheet ink. Furthermore, 3 μL of MRGO ink was dripped onto the surface of the GCE.ResultsMRGO consists of graphene layered tethered with the spherical Fe3O4. The oxygen‐based functional groups on the surface of MRGO could act as chemically active sites for the attachment of dopamine. The MRGO nanosheet has been proven to be an effective GCE modifier with a remarkable electroactive surface area of approximately 0.0104 cm2, demonstrating stable and sensitive electrochemical performance towards dopamine.ConclusionsThe MRGO nanosheets‐modified GCE presented a great potential as an electrocatalyst for dopamine detection, especially in the presence of interfering compounds like uric acid. By effectively discriminating dopamine and uric acid, MRGO nanosheets‐modified GCE have demonstrated a sensitive, stable, and specific electrochemical performance. This remarkable result underlines the immense potential of MRGO nanosheets‐modified GCE for real‐world applications, particularly in the medical field, where the ability to detect dopamine precisely and accurately is critical.

Electrochemical Determination of Epinephrine in Pharmaceutical Preparation Using Laponite Clay-Modified Graphene Inkjet-Printed Electrode.

Epinephrine (EP, also called adrenaline) is a compound belonging to the catecholamine neurotransmitter family. It can cause neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. This work describes an amperometric sensor for the electroanalytical detection of EP by using an inkjet-printed graphene electrode (IPGE) that has been chemically modified by a thin layer of a laponite (La) clay mineral. The ion exchange properties and permeability of the chemically modified electrode (denoted La/IPGE) were evaluated using multi-sweep cyclic voltammetry, while its charge transfer resistance was determined by electrochemical impedance spectroscopy. The results showed that La/IPGE exhibited higher sensitivity to EP compared to the bare IPGE. The developed sensor was directly applied for the determination of EP in aqueous solution using differential pulse voltammetry. Under optimized conditions, a linear calibration graph was obtained in the concentration range between 0.8 µM and 10 μM. The anodic peak current of EP was directly proportional to its concentration, leading to detection limits of 0.34 μM and 0.26 μM with bare IPGE and La/IPGE, respectively. The sensor was successfully applied for the determination of EP in pharmaceutical preparations. Recovery rates and the effects of interfering species on the detection of EP were evaluated to highlight the selectivity of the elaborated sensor.

Novel An Efficient Fluorescent Probe Based on Calix[4]triazacrown-5 With Naphthalimide Group for Co2+, Cd2+ and Dopamine Detection.

A novel naphthalimide-substituted calix[4]triazacrown-5 (Nap-Calix) at cone conformation was designed and synthesized to employ as a fluorescent probe, which enables the simultaneously detection of Co2+ and Cd2+ metal ions as well as dopamine (DA). 1H-NMR, 13C-NMR, ESI-MS and elemental analysis techniques were carried out to characterize its structure. Cation binding property of Nap-Calix against various metal ions such as Ba2+, Co2+, Ni2+, Pb2+, Zn2+, and Cd2+ exhibited that the sensor selectively binds to Co2+ and Cd2+ metal ions with a remarkable affinity. Introduction of Co2+ and Cd2+ metal ions to a solution of Nap-Calix in DMF/water (1:1, v/v) resulted with a new emission band at 370nm when excited at 283nm. In addition, the fluorescence sensing affinity of the probe Nap-Calix against a catecholamine neurotransmitter (dopamine) was investigated in a wide range of concentration of DA (0-0.1mmol L-1) in 50% DMF/PBS (pH = 5.0). The fluorescence intensity of Nap-Calix, with excitation/emission peaks at 283/327nm, is highly enhanced by DA. It was also observed that Nap-Calix exhibits excellent fluorescence behavior towards DA with a very low detection limit as 0.21µmol L-1.

Theoretical investigations of free energy of binding and chiral recognition studies of (R)- and (S)-Noradrenaline towards β-cyclodextrin

Noradrenaline (NA), one of the important excitatory catecholamine neurotransmitters, is used as a medication for Parkinson's Disease (PD). The β-cyclodextrin (β-CD) is one of the most effective drug carrier & also used in chiral separation. So, in this theoretical investigation, the R/S-Noradrenaline (R/S-NA) forms binding & chiral recognition mechanisms and energies with β-CD were explored. Using the AutoDock, R/S forms were first docked into the cavity of β-CD giving host-guest complexes with the free energy of binding for S-NA (−4.81 kcal/mol) larger than R-NA (−4.53 kcal/mol). The host-guest inclusion 1:1 complexes between R/S-NA and β-CD have been also modeled and optimized with ONIOM2 (B3LYP/6-31g++DP: PM6) method by using the Gaussian software. Further, frequency calculations were carried out to obtain the free energies. In comparison to the R-NA (−54.59 kcal/mol), it was observed that the S-NA (−56.48 kcal/mol) with β-CD is more stable. Furthermore, the H-bond results from molecular dynamics simulation revealed that S-NA/β-CD was more stable than R-NA/β-CD. In addition, the thermodynamic properties, vibrational analysis (IR), HOMO-LUMO band gap energy, inter molecular hydrogen bond interactions, and conformational analysis were investigated for both the R/S forms to support & compare the stability of the inclusion complex. These inclusion & high stability of S-NA/β-CD and in turn its theoretical chiral recognition behavior observed agreeing well with the reported NMR experimental data have implications in drug delivery and chiral separation research.

Neuropeptides Modulate Feeding via the Dopamine Reward Pathway.

Dopamine (DA) is a catecholamine neurotransmitter widely distributed in the central nervous system. It participates in various physiological functions, such as feeding, anxiety, fear, sleeping and arousal. The regulation of feeding is exceptionally complex, involving energy homeostasis and reward motivation. The reward system comprises the ventral tegmental area (VTA), nucleus accumbens (NAc), hypothalamus, and limbic system. This paper illustrates the detailed mechanisms of eight typical orexigenic and anorexic neuropeptides that regulate food intake through the reward system. According to recent literature, neuropeptides released from the hypothalamus and other brain regions regulate reward feeding predominantly through dopaminergic neurons projecting from the VTA to the NAc. In addition, their effect on the dopaminergic system is mediated by the prefrontal cortex, paraventricular thalamus, laterodorsal tegmental area, amygdala, and complex neural circuits. Research on neuropeptides involved in reward feeding can help identify more targets to treat diseases with metabolic disorders, such as obesity.

High-Performance FET-Based Dopamine-Sensitive Biosensor Platform Based on SOI Substrate

Dopamine is a catecholamine neurotransmitter that plays a significant role in the human central nervous system, even at extremely low concentrations. Several studies have focused on rapid and accurate detection of dopamine levels using field-effect transistor (FET)-based sensors. However, conventional approaches have poor dopamine sensitivity with values <11 mV/log [DA]. Hence, it is necessary to increase the sensitivity of FET-based dopamine sensors. In the present study, we proposed a high-performance dopamine-sensitive biosensor platform based on dual-gate FET on a silicon-on-insulator substrate. This proposed biosensor overcame the limitations of conventional approaches. The biosensor platform consisted of a dual-gate FET transducer unit and a dopamine-sensitive extended gate sensing unit. The capacitive coupling between the top- and bottom-gate of the transducer unit allowed for self-amplification of the dopamine sensitivity, resulting in an increased sensitivity of 373.98 mV/log[DA] from concentrations 10 fM to 1 μM. Therefore, the proposed FET-based dopamine sensor is expected to be widely applied as a highly sensitive and reliable biosensor platform, enabling fast and accurate detection of dopamine levels in various applications such as medical diagnosis and drug development.

Lab in tube: comparing different morphological dependent gold nanomaterials towards naked eye and optical sensing of dopamine using aptamer

ABSTRACT Dopamine is a major catecholamine neuro-transmitter that plays important function in the human central nervous system’s function. Dopamine release disorders are linked to neurological illnesses and depression. To comprehend dopamine’s physiological roles, it is vital to monitor dopamine levels at early stage or in regular basis. Many diagnostic procedures are accessible, but they have limitations, thus low-cost and simple ways to test dopamine were needed like colorimetric biosensors. Such biosensors were built with nanoparticles (gold) as a label to help identify targets and the results may be viewed with the naked eye. These gold nanomaterials are available in a range of morphologies, including nanoparticles, nanorods, and others. The present method reported the use of gold nanoparticles (GNPs) and gold nanorods (GNRs) for effective aptamer-based sensing of dopamine. Herein a comparison study was conducted between GNPs and GNRs based apta-sensing of dopamine. Both AuNPs (gold nanoparticles) and AuNRs (gold nanorods) were characterised by SEM (Scanning electron microscope), XRD (X-Ray diffraction) and UV-Vis spectrophotometer (Ultraviolet-Visible spectroscopy). The result claimed that GNRs are more sensitive as they were detecting low concentration of dopamine which was confirmed via UV analysis. Various other parameters such as change in salt concentration, incubation time and interferents were also studied which proved that utilising aptamer and gold-nanorods can be a promising material in the neurotransmitter based diagnosis.

Cross-linkage induced fluorescence: Fabrication of fluorescent organic particles via reaction between polyethyleneimine and dopamine-containing copolymers

Dopamine is the most abundant catecholamine neurotransmitter in the brain and has extensive applications in biomedicine and materials science. Here, novel metal-free fluorescent organic particles (FOPs) with excellent biocompatibility and high photostability, namely DA-PEG-PEI, were successfully synthesized through combination of ring-opening reaction and crosslinking reaction between polyethyleneimine (PEI) and dopamine-containing copolymers (DA-PEGDGE). Because of the crosslink-enhanced emission (CEE) effect of PEI and a quantity of functional groups such as catechol and amines on the surface of the particles, DA-PEG-PEI FOPs possessed high water dispersibility and superior optical properties, making them highly potential for biological imaging applications. Moreover, owing to the existence of functional components/groups, such as amines, catechol groups, the resultant DA-PEG-PEI FOPs can be potentially applied for loading or carrying different bioactive molecules, such as anticancer agent bortezomib, siRNA and CPG oligodeoxynucleotide through formation of dynamic bonds or electrostatic interaction. Furthermore, this reaction can occur under ambient environment, room temperature, in the present of oxygen and without catalysts. Therefore, we believe that this work could not only provide a simple and elegant route for preparation of FOPs, but also have great potential for construction of multifunctional theranostic platforms.

Deuterium Solvent Kinetic Isotope Effect on Enzymatic Methyl Transfer Catalyzed by Catechol O-methyltransferase.

Catechol o-methyltransferase plays a key role in the metabolism of catecholamine neurotransmitters. At present, its catalytic mechanism, overall structure, and kinetic characteristics have been basically clarified, but few people have paid attention to the function of solvents on enzymatic methyl transfer reactions. The influence of solvents on enzymatic reactions has always been a fuzzy hot topic. In addition, as a well-studied typical methyltransferase, COMT is a good test bed for exploring the source of the solvent isotope effect, which is a powerful tool in enzymatic mechanism research. We have measured the kinetic parameters of methyl transfer catalyzed by COMT in both normal water (H2O) and heavy water (D2O) by high-performance liquid chromatography (HPLC) in the range of pL 6 ~ 11. The kinetic characteristics of COMT in H2O and D2O were significantly different under different pH/pD conditions. Significant solvent kinetic isotope effects (SKIE) were obtained, especially inverse solvent kinetic isotope effects (SKIE < 1) were observed in this methyl transfer reaction for the first time. Traditional factors which could interpret the solvent isotope effect were ruled out. It's suggested that the solvent might affect the overall conformation as well as the flexibility of protein through non-covalent forces, thus altering the catalytic activity of COMT and leading to the solvent isotope effect.

Nanoscale Zinc-Based Metal-Organic Frameworks Induce Neurotoxicity by Disturbing the Metabolism of Catecholamine Neurotransmitters.

As a group of new nanomaterials, nanoscale metal-organic frameworks (MOFs) are widely applied in the biomedical field, exerting unknown risks to the human body, especially the central nervous system. Herein, the impacts of MOF-74-Zn nanoparticles on neurological behaviors and neurotransmitter metabolism are explored in both in vivo and in vitro assays modeled by C57BL/6 mice and PC12 cells, respectively. The mice exhibit increased negative-like behaviors, as demonstrated by the observed decrease in exploring behaviors and increase in despair-like behaviors in the open field test and forced swimming test after exposure to low doses of MOF-74-Zn nanoparticles. Disorders in the catecholamine neurotransmitter metabolism may be responsible for the MOF-74-Zn-induced abnormal behaviors. Part of the reason for this is the inhibition of neurotransmitter synthesis caused by restrained neurite extension. In addition, MOF-74-Zn promotes the translocation of more calcium into the cytoplasm, accelerating the release and uptake and finally resulting in an imbalance between synthesis and catabolism. Taken together, the results from this study indicate the human toxicity risks of nanoscale low-toxicity metal-based MOFs and provide valuable insight into the rational and safe use of MOF nanomaterials.

Intracerebral Fluorescence-Photoacoustic Dual-Mode Imaging for Precise Diagnosis and Drug Intervention Tracing in Depression.

Unravelling the pathophysiology of depression is a unique challenge. Depression is closely associated with reduced norepinephrine (NE) levels; therefore, developing bioimaging probes to visualize NE levels in the brain is a key to elucidating the pathophysiological process of depression. However, because NE is similar in structure and chemical properties to two other catecholamine neurotransmitters, epinephrine and dopamine, designing an NE-specific multimodal bioimaging probe is a difficult task. In this work, we designed and synthesized the first near-infrared fluorescent-photoacoustic (PA) dual-modality imaging probe for NE (FPNE). The β-hydroxyethylamine of NE was shown to react via nucleophilic substitution and intramolecular nucleophilic cyclization, resulting in the cleavage of a carbonic ester bond in the probe molecule and release of a merocyanine molecule (IR-720). This process changed the color of the reaction solution from blue-purple to green, and the absorption peak was red-shifted from 585 to 720 nm. Under light excitation at 720 nm, linear relationships between the concentration of NE and both the PA response and the fluorescence signal intensity were observed. Thus, the use of intracerebral in situ visualization for diagnosis of depression and monitoring of drug interventions was achieved in a mouse model by fluorescence and PA imaging of brain regions after administration of FPNE by tail-vein injection.

Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark.

In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide. We now show that the dark process is not limited to the unusual structural molecule melanin: signaling biomolecules such as indolamine and catecholamine neurotransmitters and hormones can also be chemiexcited to energy levels high enough to form dCPDs. Oxidation of serotonin, dopamine, melatonin, and related biogenic amines by peroxynitrite created triplet-excited species, evidenced by chemiluminescence, energy transfer to a triplet-state reporter, or transfer to O2 resulting in singlet molecular oxygen. For a subset of these signaling molecules, triplet states created by peroxynitrite or peroxidase generated dCPDs at levels comparable to ultraviolet (UV). Neurotransmitter catabolism by monoamine oxidase also generated dCPDs. These results reveal a large class of signaling molecules as electronically excitable by biochemical reactions and thus potential players in deviant mammalian metabolism in the absence of light.

Flexible electroactive membranes for the electrochemical detection of dopamine

In addition of a key catecholamine neurotransmitter, dopamine is is the metabolite predominantly produced by specific types of tumors (e.g. paragangliomas and neuroblastomas), which cannot be diagnosed using conventional sensitive tests. Within this context, development of flexible electrochemical sensors to monitor dopamine levels in physiological fluids for the early diagnosis and control of diseases related to abnormal levels of such compound, is necessary. In this work, a flexible self-supported membrane, which acts directly as electrode, has been developed to detect dopamine. The membrane consists of three nanoperforated polylactic acid (PLA) layers, which provide flexibility and mechanical integrity, separated by two layers of an electroactive copolymer, which are obtained by electrochemical copolymerization of 3,4-ethylenedioxythiophene and aniline. The sensitivity and detection limit provided by the electroactive copolymer, which is accessible to dopamine molecules through the nanoperforations of the PLA outer layers, is 1.846 µA/(cm2·µM) and 1.7 µM, respectively, in a urea-rich environments that mimics urine. These values allow us to propose the self-standing flexible electrodes developed in this study for the detection of dopamine in patients affected by paragangliomas and neuroblastomas tumors, which typically present dopamine concentrations between 2 and 7 μM.

Advanced Nanomaterials-Based Electrochemical Biosensors for Catecholamines Detection: Challenges and Trends.

Catecholamines, including dopamine, epinephrine, and norepinephrine, are considered one of the most crucial subgroups of neurotransmitters in the central nervous system (CNS), in which they act at the brain's highest levels of mental function and play key roles in neurological disorders. Accordingly, the analysis of such catecholamines in biological samples has shown a great interest in clinical and pharmaceutical importance toward the early diagnosis of neurological diseases such as Epilepsy, Parkinson, and Alzheimer diseases. As promising routes for the real-time monitoring of catecholamine neurotransmitters, optical and electrochemical biosensors have been widely adopted and perceived as a dramatically accelerating development in the last decade. Therefore, this review aims to provide a comprehensive overview on the recent advances and main challenges in catecholamines biosensors. Particular emphasis is given to electrochemical biosensors, reviewing their sensing mechanism and the unique characteristics brought by the emergence of nanotechnology. Based on specific biosensors' performance metrics, multiple perspectives on the therapeutic use of nanomaterial for catecholamines analysis and future development trends are also summarized.

Quantification of catecholamine neurotransmitters released from cutaneous vasoconstrictor nerve endings in men with cervical spinal cord injury.

Control of cutaneous circulation is critically important to maintain thermoregulation, especially in individuals with cervical spinal cord injury (CSCI) who have no or less central thermoregulatory drive. However, the peripheral vasoconstrictor mechanism and capability have not been fully investigated after CSCI. Post- and presynaptic sensitivities of the cutaneous vasoconstrictor system were investigated in 8 CSCI and 7 sedentary able-bodied (AB) men using an intradermal microdialysis technique. Eight doses of norepinephrine (NE, 10-8 to 10-1 M) and five doses of tyramine (TY, 10-8, 10-5 to 10-2 M) were administered into the anterior right and left thigh, respectively. Endogenous catecholamines, noradrenaline, and dopamine, collected at the TY site, were determined by high-performance liquid chromatography with electrochemical detection. Regardless of vasoconstrictor agents, cutaneous vascular conductance decreased dose-dependently and responsiveness was similar between the groups (NE: Group P = 0.255, Dose P = 0.014; TY: Group P = 0.468, Dose P < 0.001), whereas the highest dose of each drug induced cutaneous vasodilation. Administration of TY promoted the release of noradrenaline and dopamine in both groups. Notably, the amount of noradrenaline released was similar between the groups (P = 0.819), although the concentration of dopamine was significantly greater in individuals with CSCI than in AB individuals (P = 0.004). These results suggest that both vasoconstrictor responsiveness and neural functions are maintained after CSCI, and dopamine in the skin is likely to induce cutaneous vasodilation.

Culture of leukocyte-derived cells from human peripheral blood: Increased expression of pluripotent genes OCT4, NANOG, SOX2, self-renewal gene TERT and plasticity.

There are few stem cells in human peripheral blood (PB). Increasing the population and plasticity of stem cells in PB and applying it to regenerative medicine require suitable culture methods. In this study, leukocyte populations 250 mL of PB were collected using a blood separator before that were cultured in optimal cell culture medium for 4 to 7 days. After culturing, stemness characteristics were analyzed, and red blood cells were removed from the cultured cells. In our results, stemness markers of the leukocyte populations Sca-1+ CD45+, CD117+ CD45+, and very small embryonic-like stem cells CD34+ Lin- CD45- and CXCR4+ Lin- CD45- were significantly increased. Furthermore, the expression of stem cell genes OCT4 (POU5F1), NANOG, SOX2, and the self-renewal gene TERT was analyzed by quantitative real-time polymerase chain reaction in these cells, and it showed a significant increase. These cells could be candidates for multi-potential cells and were further induced using trans-differentiation culture methods. These cells showed multiple differentiation potentials for osteocytes, nerve cells, cardiomyocytes, and hepatocytes. These results indicate that appropriate culture methods can be applied to increase expression of pluripotent genes and plasticity. Leukocytes of human PB can be induced to trans-differentiate into pluripotent potential cells, which will be an important breakthrough in regenerative medicine.

The Dopamine D1 Receptor Attenuates Titanium Particle-Induced Inhibition of Osteogenesis by Activating the Wnt Signaling Pathway.

Periprosthetic osteolysis (PPO), caused by wear particles, has become a major cause of joint replacement failure. Secondary surgery after joint replacement poses a serious threat to public health worldwide. Therefore, determining how to effectively inhibit wear particle-induced PPO has become an urgent issue. Recently, the interaction between osteogenic inhibition and wear particles at the biological interface of the implant has been found to be an important factor in the pathological process. Previous studies have found that the central nervous system plays an important role in the regulation of bone formation and bone remodeling. Dopamine (DA), an important catecholamine neurotransmitter, plays an integral role in the physiological and pathological processes of various tissues through its corresponding receptors. Our current study found that upregulation of dopamine first receptors could be achieved by activating the Wnt/β-catenin pathway, improving osteogenesis in vivo and in vitro, and significantly reducing the inhibition of titanium particle-induced osteogenesis. Overall, these findings suggest that dopamine first receptor (D1R) may be a plausible target to promote osteoblast function and resist wear particle-induced PPO.

In Silico Investigation of the Human GTP Cyclohydrolase 1 Enzyme Reveals the Potential of Drug Repurposing Approaches towards the Discovery of Effective BH4 Therapeutics.

The GTP cyclohydrolase 1 enzyme (GTPCH1) is the rate-limiting enzyme of the tetrahydrobiopterin (BH4) biosynthetic pathway. Physiologically, BH4 plays a crucial role as an essential cofactor for the production of catecholamine neurotransmitters, including epinephrine, norepinephrine and dopamine, as well as the gaseous signaling molecule, nitric oxide. Pathological levels of the cofactor have been reported in a number of disease states, such as inflammatory conditions, neuropathic pain and cancer. Targeting the GTPCH1 enzyme has great potential in the management of a number of disease pathologies associated with dysregulated BH4 physiology. This study is an in silico investigation of the human GTPCH1 enzyme using virtual screening and molecular dynamic simulation to identify molecules that can be repurposed to therapeutically target the enzyme. A three-tier molecular docking protocol was employed in the virtual screening of a comprehensive library of over 7000 approved medications and nutraceuticals in order to identify hit compounds capable of binding to the GTPCH1 binding pocket with the highest affinity. Hit compounds were further verified by molecular dynamic simulation studies to provide a detailed insight regarding the stability and nature of the binding interaction. In this study, we identify a number of drugs and natural compounds with recognized anti-inflammatory, analgesic and cytotoxic effects, including the aminosalicylate olsalazine, the antiepileptic phenytoin catechol, and the phlorotannins phlorofucofuroeckol and eckol. Our results suggest that the therapeutic and clinical effects of hit compounds may be partially attributed to the inhibition of the GTPCH1 enzyme. Notably, this study offers an understanding of the off-target effects of a number of compounds and advocates the potential role of aminosalicylates in the regulation of BH4 production in inflammatory disease states. It highlights an in silico drug repurposing approach to identify a potential means of safely targeting the BH4 biosynthetic pathway using established therapeutic agents.

Multicolor colorimetric detection of dopamine based on iodide-responsive copper-gold nanoparticles.

Dopamine (DA) is one of the most essential catecholamine neurotransmitters in the human body. A rapid colorimetric detection method for DA in urine and serum was established in this work using unmodified iodide-responsive copper-gold nanoparticles (Cu-Au NPs). The detection method provides a rapid response with color variability within 15 min at room temperature. In addition, the colorimetric probe has elevated stability, excellent selectivity and resistance to interference.

Machine-learning assisted multiplex detection of catecholamine neurotransmitters with a colorimetric sensor array.

Catecholamine neurotransmitters (CNs), such as dopamine (DA), epinephrine (EP), norepinephrine (NEP), and levodopa (LD), are recognized as the primary biomarkers of a variety of neurological illnesses. Therefore, simultaneous monitoring of these biomarkers is highly recommended for clinical diagnosis and treatment. In this study, a high-performance colorimetric artificial tongue has been proposed for the multiplex detection of CNs. Different aggregation behaviors of gold nanoparticles in the presence of CNs under various buffering conditions generate unique fingerprint response patterns. Under various buffering conditions, the distinct acidity constants of CNs, and consequently their predominant species at a given pH, drive the aggregation of gold nanoparticles (AuNPs). The utilization of machine learning algorithms in this design enables classification and quantification of CNs in various samples. The response profile of the array was analyzed using the linear discriminant analysis algorithm for classification of CNs. This colorimetric sensor array is capable of accurately distinguishing between individual neurotransmitters and their combinations. Partial least squares regression was also applied for quantitation purposes. The obtained analytical figures of merit (FOMs) and linear ranges of 0.6-9 μM (R2 = 0.99) for DA, 0.1-10 μM (R2 = 0.99) for EP, 0.1-9 μM (R2 = 0.99) for NEP and 1-70 μM (R2 = 0.99) for LD demonstrated the potential applicability of the developed sensor array in precise and accurate determination of CNs. Finally, the feasibility of the array was validated in human urine samples as a complex biological fluid with LODs of 0.3, 0.5, 0.2, and 1.9 μM for DA, EP, NEP, and LD, respectively.