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| 1 | Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays显示文摘Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies. | Niccolo Candelise Matthias Schmitz Katrin Thüne Maria Cramm Alberto Rabano Saima Zafar Erik Stoops Hugo Vanderstichele Anna Villar-Pique Franc Llorens Inga Zerr | 2020 | Translational Neurodegeneration2020，9，1： | 1 |
| 2 | Ecto-GPR37:a potential biomarker for Parkinson’s disease显示文摘Objective:a-Synuclein has been studied as a potential biomarker for Parkinson's disease(PD)with no concluding results.Accordingly,there is an urgent need to find out reliable specific biomarkers for PD.GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism.Here,we investigated whether GPR37 is upregulated in sporadic PD,and thus a suitable potential biomarker for PD.Methods:GPR37 protein density and mRNA expression in postmortem substantia nigra(SN)from PD patients were analysed by immunoblot and RT-qPCR,respectively.The presence of peptides from the N-terminus-cleaved domain of GPR37(i.e.ecto-GPR37)in human cerebrospinal fluid(CSF)was determined by liquid chromatography-mass spectrometric analysis.An engineered in-house nanoluciferase-based immunoassay was used to quantify ecto-GPR37 in CSF samples from neurological control(NC)subjects,PD patients and Alzheimer's disease(AD)patients.Results:GPR37 protein density and mRNA expression were significantly augmented in sporadic PD.Increased amounts of ecto-GPR37 peptides in the CSF samples from PD patients were identified by mass spectrometry and quantified by the in-house ELISA method.However,the CSF total a-synuclein level in PD patients did not differ from that in NC subjects.Similarly,the cortical GPR37 mRNA expression and CSF ecto-GPR37 levels in AD patients were also unaltered.Conclusion:GPR37 expression is increased in SN of sporadic PD patients.The ecto-GPR37 peptides are significantly increased in the CSF of PD patients,but not in AD patients.These results open perspectives and encourage further clinical studies to confirm the validity and utility of ecto-GPR37 as a potential PD biomarker. | Xavier Morato Paula Garcia-Esparcia Josep Argerich Franc Llorens Inga Zerr Wojciech Paslawski Eva Borras Eduard Sabido Ulla EPetaja-Repo Victor Fernandez-Duenas Isidro Ferrer Per Svenningsson Francisco Ciruela | 2021 | Translational Neurodegeneration2021，10，1： | 1 |
| 3 | Cerebrospinal fluid neurogranin as a new player in prion disease diagnosis and prognosis显示文摘Neurogranin (Ng) and its role as Alzheimer’s disease (AD) biomarker: Ng is a calmodulin-binding protein mainly expressed in cerebral structures such as the cortex,hippocampus and striatum.It is mainly located in the dendritic processes,particularly in post-synaptic compartments,but also in the cytosolic compartment,being likely involved in the regulation of the intracellular calcium-calmodulin signaling pathway (Represa et al.,1990).In the last decade,a plethora of studies have demonstrated that cerebrospinal fluid (CSF) Ng is increased in AD patients and in individuals with an ADlike CSF profile (Kester et al.,2015a).This increase seems to be disease-specific because other neurodegenerative conditions including frontotemporal dementia,Lewy body dementia,Parkinson’s disease,progressive supranuclear palsy,multiple system atrophy or Huntington’s disease,present CSF Ng concentrations similar to controls (Wellington et al.,2016).Ng levels in CSF appear to be elevated in mild cognitive impairment (MCI)-affected individuals who progress to AD and are highly related to memory and cognitive function (Kester et al.,2015a;Tarawneh et al.,2016),which indicates that this protein may serve as an early AD biomarker with diagnostic utility in pre-dementia disease stages,and with prognostic utility to predict cognitive decline and MCI-to-AD conversion. | Anna Villar-Piqué Inga Zerr Franc Llorens | 2020 | Neural Regeneration Research2020，15，5： | 1 |
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