Production of a monoclonal antibody, against human α-synuclein, in a subpopulation of C57BL/6J mice, presenting a deletion of the α-synuclein locus

Mougenot, Anne-Laure; Bétemps, Dominique; Hogeveen, Kevin; Kovács, Gábor G.; Chouaf-Lakhdar, Latifa; Milhavet, Ollivier; Lehmann, Sylvain; Legastelois, Stéphane; Pin, Jean-Jacques; Baron, Thierry

doi:10.1016/j.jneumeth.2010.08.010

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…Of interest, these differentiating profiles revealed the unique presence of proteins associated with Parkinson's disease namely: aSyn and PARK7 [34], [35], [37], [38], [39]. The presence of aSyn in PDAC has not been reported in the literature and previous mouse/drosophila models for this protein have not reported alterations in pancreas function or incidence of pancreatic cancer [43], [44], [45]. However, elevated expression of aSyn has been recently reported in melanoma [46], while its isoform gamma-synuclein (γSyn) a.k.a.…”

Section: Discussionmentioning

confidence: 99%

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

et al. 2011

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Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

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Section: Discussionmentioning

confidence: 99%

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

et al. 2011

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“…Aggregated α‐syn, formed by treatment with either high salt or acid conditions, generated antibodies with high reactivity to disease associated α‐syn (Mougenot et al . ; Kovacs et al . ).…”

Section: α‐Syn Specific Antibodies: Invaluable Tools For Synucleinopamentioning

confidence: 99%

Antibodies against alpha‐synuclein: tools and therapies

Vaikath

Hmila

Gupta

et al. 2019

Journal of Neurochemistry

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Synucleinopathies including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are characterized by the abnormal accumulation and propagation of α‐synuclein (α‐syn) pathology in the central and peripheral nervous system as Lewy bodies or glial cytoplasmic inclusions. Several antibodies against α‐syn have been developed since it was first detected as the major component of Lewy bodies and glial cytoplasmic inclusions. Over the years, researchers have generated specific antibodies that alleviate the accumulation of intracellular aggregated α‐syn and associated pathology in cellular and preclinical models of synucleinopathies. So far, antibodies have been the first choice as tools for research and diagnosis and currently, a wide variety of antibody fragments have been developed as an alternative to full‐length antibodies for increasing its therapeutic usefulness. Recently, conformation specific antibody‐based approaches have been found to be promising as therapeutic strategies, both to block α‐syn aggregation and ameliorate the resultant cytotoxicity, and as diagnostic tools. In this review, we summarize different α‐syn specific antibodies and provide their usefulness in tackling synucleinopathies. This article is part of the Special Issue “Synuclein”.

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“…This suggests that AS pathology revealed by immunohistochemistry might not be caused by AS accumulation but rather by conformational changes. Different mono-and polyclonal antibodies that bind specifically to AS have been described [344][345][346][347][348][349][350][351][352][353].…”

Section: α-Synuclein and Neurodegenerationmentioning

confidence: 99%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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Genetic, neuropathological and biochemical evidence implicates α-synuclein, a 140 amino acid presynaptic neuronal protein, in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. The aggregated protein inclusions mainly containing aberrant α-synuclein are widely accepted as morphological hallmarks of α-synucleinopathies, but their composition and location vary between disorders along with neuronal networks affected. α-Synuclein exists physiologically in both soluble and membran-bound states, in unstructured and α-helical conformations, respectively, while posttranslational modifications due to proteostatic deficits are involved in β-pleated aggregation resulting in formation of typical inclusions. The physiological function of α-synuclein and its role linked to neurodegeneration, however, are incompletely understood. Soluble oligomeric, not fully fibrillar α-synuclein is thought to be neurotoxic, main targets might be the synapse, axons and glia. The effects of aberrant α-synuclein include alterations of calcium homeostasis, mitochondrial dysfunction, oxidative and nitric injuries, cytoskeletal effects, and neuroinflammation. Proteasomal dysfunction might be a common mechanism in the pathogenesis of neuronal degeneration in α-synucleinopathies. However, how α-synuclein induces neurodegeneration remains elusive as its physiological function. Genome wide association studies demonstrated the important role for genetic variants of the SNCA gene encoding α-synuclein in the etiology of Parkinson's disease, possibly through effects on oxidation, mitochondria, autophagy, and lysosomal function. The neuropathology of synucleinopathies and the role of α-synuclein as a potential biomarker are briefly summarized. Although animal models provided new insights into the pathogenesis of Parkinson disease and multiple system atrophy, most of them do not adequately reproduce the cardinal features of these disorders. Emerging evidence, in addition to synergistic interactions of α-synuclein with various pathogenic proteins, suggests that prionlike induction and seeding of α-synuclein could lead to the spread of the pathology and disease progression. Intervention in the early aggregation pathway, aberrant cellular effects, or secretion of α-synuclein might be targets for neuroprotection and disease-modifying therapy.

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Production of a monoclonal antibody, against human α-synuclein, in a subpopulation of C57BL/6J mice, presenting a deletion of the α-synuclein locus

Cited by 11 publications

References 35 publications

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Antibodies against alpha‐synuclein: tools and therapies

The role of α-synuclein in neurodegeneration — An update

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