detection-disease-associated-synuclein-enhanced-elisa-brain

Detection of Disease-associated &#945;-synuclein by Enhanced ELISA in the Brain of Transgenic Mice Overexpressing Human A53T Mutated &#945;-synuclein

In addition to established methods like Western blot, new methods are needed to quickly and easily quantify disease-associated &#945;-synuclein (&#945;SD) ...

ANSES - French Agency for Food, Environmental and Occupational Health & Safety

The accumulation of misfolded proteins appears as a fundamental pathogenic process in human neurodegenerative diseases. In the case of synucleinopathies such as Parkinson's disease (PD) or dementia with Lewy bodies (DLB), the intraneuronal deposition of aggregated alpha-synuclein (αS) is a major characteristic of the disease, but the molecular basis distinguishing the disease-associated protein (αSD) from its normal counterpart remains poorly understood. However, recent research suggests that a prion-like mechanism could be involved in the inter-cellular and inter-molecular propagation of aggregation of the protein within the nervous system.

Alpha-synuclein spreading in M83 mice brain revealed by detection of pathological α-synuclein by enhanced ELISA.

Mycoplasma mycoides subsp. mycoides (Mmm) strain Afadé had previously been shown to undergo spontaneous phase variations between an opaque capsulated variant and a translucent (TR) variant devoid of a capsule but able to secrete cell-free exopolysaccharides. This phase variation is associated with an ON/OFF genetic switch in a glucose permease gene. In this study, in vivo and in vitro assays were conducted to compare the virulence of the two variants and their abilities to resist host defence. Capsulated variants were shown, in a mouse model, to induce longer bacteraemia that was correlated with better serum resistance in vitro. In contrast, TR variants displayed better ability to adhere to an inert support, linked to the absence of a capsule, changes in cell surface hydrophobicity and increased resistance to antimicrobial peptide and hydrogen peroxide. The switch from one variant population to another, which was observed both in vivo and in vitro under stress conditions, is further discussed as a means for Mmm to modulate its interactions with animal hosts during different stages of the disease.

Comparison of in vivo and in vitro properties of capsulated and noncapsulated variants of Mycoplasma mycoides subsp. mycoides strain Afadé: a potential new insight into the biology of contagious bovine pleuropneumonia.

Alpha-synuclein is a key protein in Parkinson disease (PD) and dementia with Lewy bodies. It is found in Lewy bodies in the brains of PD patients and has been reported in the peripheral nervous system in postmortem tissues from PD patients and in biopsies from patients in the preclinical phase of PD. Here, we used a transgenic mouse model of human synucleinopathies expressing the A53T mutant α-synuclein (TgM83) in which a neurodegenerative process associated with α-synuclein occurs spontaneously and increases with age. In particular, α-synuclein protein phosphorylated at serine 129 (pSer129 α-synuclein) naturally and progressively increases in diseased brains. We examined the time course of pSer129 α-synuclein presence in the gut of these mice between 1.5 and 22 months of age using immunohistochemistry and paraffin-embedded tissue blots. The pSer129 α-synuclein accumulated early (before the onset of motor signs) and persistently in the enteric nervous system and was concomitantly found in the brain. These results suggest that the accumulation of phosphorylated α-synuclein in the enteric and central nervous systems may result from parallel pathologic processes when the disease is linked to a mutation of α-synuclein.

Article	Year
Alpha-synuclein spreading in M83 mice brain revealed by detection of pathological α-synuclein by enhanced ELISA. Acta neuropathologica communications\| PubMed ID: 24624994	2014
Comparison of in vivo and in vitro properties of capsulated and noncapsulated variants of Mycoplasma mycoides subsp. mycoides strain Afadé: a potential new insight into the biology of contag... FEMS microbiology letters\| PubMed ID: 25123820	2014
Early and persistent expression of phosphorylated α-synuclein in the enteric nervous system of A53T mutant human α-synuclein transgenic mice. Journal of neuropathology and experimental neurology\| PubMed ID: 25383638	2014

Latifa Lakhdar

Biography

JoVE Journal Publications

Other Publications