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. 2020 Jun 17;14:626. doi: 10.3389/fnins.2020.00626

FIGURE 2.

FIGURE 2

Possibilities to extend of αS-detection methods in GIT tissues of PD patients or animal models. Each method has its limits, so in order to find a reliable method of PD diagnosis, a more comprehensive approach to the analysis of studied tissues is necessary. In contrast to conventional immunohistochemistry, immunohistochemical analysis of whole-mount tissues provides a more comprehensive view of the processes taking place in the studied tissue under. The conformation-specific antibody may significantly improve the ability to detect pathological αS, as the detection of total αS, or its phosphorylated form, does not appear to be sufficient at present. These can be used not only for immunohistochemical or biochemical analyzes and, together with various currently widely available signal amplification systems, they can increase not only the specificity but also the sensitivity of the given methods. PMCA appears to be very versatile and specific in detecting αS pathological forms, as well as in distinguishing individual pathological αS strains. Imaging methods may rely on the continuous development of either fluorescent probes or the development of the methodologies themselves. Luminescent-conjugated oligothiophenes (LCO) represent a new generation of probes with the ability to detect a broader spectrum of protein aggregate proteins, compared to conventional probes. In addition, based on changes in emission spectra, they also provide information on the conformation of the studied aggregated proteins. Fluorescent lifetime imaging (FLIM) reflects the qualitative changes near fluorophore, and therefore with higher sensitivity can detect very small, such as conformational, changes. Although the role of the intestinal microbiome in the PD pathogenesis is currently unclear, analysis of the intestinal microbiota, inflammatory response or permeability of the intestinal barrier can provide a more comprehensive view of the processes taking place in the GIT.