1. A Label-Free Sensor Array Based on Carbon Quantum Dots for Detection of α-Synuclein Oligomers in Saliva.
期刊:Analytical chemistry
日期:2024-07-22
DOI :10.1021/acs.analchem.4c00874
Salivary oligomeric α-synuclein (α-Syn) has been introduced as a promising biomarker for the diagnosis of Parkinson's disease. Herein, a fluorescence sensor array based on three carbon quantum dots (CQDs) with different surface functional groups was developed for the identification and quantification of salivary α-Syn oligomers. Each of the CQDs generated a different fluorescence response to the target analyte, and the responses were analyzed by NPLS-DA to create a unique response pattern for the target analyte. The developed three-element sensor array showed a linear response to α-Syn oligomers in the range of 0.5-32 μg/mL and a detection limit (LOD) of 0.5 μg/mL, with a cross-validation accuracy of 92% in aqueous solution. The sensor array could detect the analyte in a mixture of different proteins and in the complex medium of saliva, with the LOD of 0.3 μg/mL indicating the massive potential of CQD arrays for developing sensitive, simple, inexpensive, and label-free sensing platforms.
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2区Q1影响因子: 4.6
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2. Neuronal Bmi-1 is critical for melatonin induced ubiquitination and proteasomal degradation of α-synuclein in experimental Parkinson's disease models.
作者:Srivastava Anup K , Choudhury Subhasree Roy , Karmakar Surajit
期刊:Neuropharmacology
日期:2020-11-04
DOI :10.1016/j.neuropharm.2020.108372
Epigenetic polycomb repressor complex-1 subunit BMI-1 plays a pivotal role in the process of gene repression to maintain the self-renewal and differentiation state of neurogenic tissues. Accumulating reports links lower expression of BMI-1 fails to regulate the repression of anti-oxidant response genes disrupt mitochondrial homeostasis underlying neurodegeneration. Interestingly, this negative relation between BMI-1 function and neurodegeneration is distinct but has not been generalized as a potential biomarker particularly in Parkinson's disease (PD). Hyperphosphorylated BMI-1 undergoes canonical polycomb E3 ligase function loss, thereby leads to reduce monoubiquitylation of histone 2A at lysine 119 (H2AK119ub) corroborates cellular accumulation of α-synuclein protein phosphorylated at serine 129 (pα-SYN (S129). In general, neuroprotectant suppressing pα-SYN (S129) level turns ineffective upon depletion of neuronal BMI-1. However, it has been observed that our neuroprotectant exposure suppresses the cellular pα-SYN (S129) and restore the the BMI-1 expression level in neuronal tissues. The pharmacological inhibition and activation of proteasomal machinery promote the cellular accumulation and degradation of neuronal pα-SYN (S129), respectively. Furthermore, our investigation reveals that accumulated pα-SYN (S129) are priorly complexed with BMI-1 undergoes ubiquitin-dependent proteasomal degradation and established as key pathway for therpeutic effect in PD. These findings linked the unestablished non-canonical role of BMI-1 in the clearance of pathological α-SYN and suspected to be a novel therapeutic target in PD.
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1区Q1影响因子: 16
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3. Single-Molecule Detection of α-Synuclein Oligomers in Parkinson's Disease Patients Using Nanopores.
期刊:ACS nano
日期:2023-11-10
DOI :10.1021/acsnano.3c08456
α-Synuclein (α-Syn) is an intrinsically disordered protein whose aggregation in the brain has been significantly implicated in Parkinson's disease (PD). Beyond the brain, oligomers of α-Synuclein are also found in cerebrospinal fluid (CSF) and blood, where the analysis of these aggregates may provide diagnostic routes and enable a better understanding of disease mechanisms. However, detecting α-Syn in CSF and blood is challenging due to its heterogeneous protein size and shape, and low abundance in clinical samples. Nanopore technology offers a promising route for the detection of single proteins in solution; however, the method often lacks the necessary selectivity in complex biofluids, where multiple background biomolecules are present. We address these limitations by developing a strategy that combines nanopore-based sensing with molecular carriers that can specifically capture α-Syn oligomers with sizes of less than 20 nm. We demonstrate that α-Synuclein oligomers can be detected directly in clinical samples, with minimal sample processing, by their ion current characteristics and successfully utilize this technology to differentiate cohorts of PD patients from healthy controls. The measurements indicate that detecting α-Syn oligomers present in CSF may potentially provide valuable insights into the progression and monitoring of Parkinson's disease.
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2区Q2影响因子: 3.9
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4. Preparation and Characterization of Stable α-Synuclein Lipoprotein Particles.
作者:Eichmann Cédric , Campioni Silvia , Kowal Julia , Maslennikov Innokentiy , Gerez Juan , Liu Xiaoxia , Verasdonck Joeri , Nespovitaya Nadezhda , Choe Senyon , Meier Beat H , Picotti Paola , Rizo Josep , Stahlberg Henning , Riek Roland
期刊:The Journal of biological chemistry
日期:2016-02-04
DOI :10.1074/jbc.M115.707968
Multiple neurodegenerative diseases are caused by the aggregation of the human α-Synuclein (α-Syn) protein. α-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that α-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of α-Syn and anionic phospholipids. These particles are called α-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the α-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid-state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that α-Syn adopts a helical secondary structure within these particles. Based on cryo-electron microscopy (cryo-EM) and dynamic light scattering (DLS) α-Syn lipoprotein particles have a defined size with a diameter of ∼23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of α-Syn particles reveal a high-order protein-lipid entity composed of ∼8-10 α-Syn molecules. The close resemblance in size between cross-linked in vitro-derived α-Syn lipoprotein particles and a cross-linked species of endogenous α-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of α-Syn lipoprotein nanoparticles.