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VAPB ER-Aggregates, A Possible New Biomarker in ALS Pathology

1
Department of Medical Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
2
Department of Medical Sciences and Public Health, University of Cagliari, S. P. Monserrato—Sestu km 0,700, 09042 Monserrato, Italy
3
Institute of Neuropathology, RWTH Aachen University Medical School, Pauwelsstr. 30, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 164; https://doi.org/10.3390/cells9010164
Received: 25 November 2019 / Revised: 16 December 2019 / Accepted: 30 December 2019 / Published: 9 January 2020
A point mutation (P56S) in the gene-encoding vesicle-associated membrane-protein-associated protein B (VAPB) leads to an autosomal-dominant form of amyotrophic lateral sclerosis (ALS), classified as ALS-8. The mutant VAPB is characterized by ER-associated aggregates that lead to a complete reorganization of ER structures. Growing evidences suggest VAPB involvement in ALS pathomechanisms. In fact, numerous studies demonstrated VAPB alteration also in sporadic ALS (sALS) and showed the presence of its aggregates when others ALS-related gene are mutant. Recently, the identification of new biomarkers in peripheral blood mononuclear cells (PBMCs) has been proposed as a good noninvasive option for studying ALS. Here, we evaluated VAPB as a possible ALS pathologic marker analyzing PBMCs of sALS patients. Immunofluorescence analysis (IFA) showed a peculiar pattern of VAPB aggregates in sALS, not evident in healthy control (HC) subjects and in Parkinson’s disease (PD) PBMCs. This specific pattern led us to suppose that VAPB could be misfolded in sALS. The data indirectly confirmed by flow cytometry assay (FCA) showed a reduction of VAPB fluorescent signals in sALS. However, our observations were not associated with the presence of a genetic mutation or altered gene expression of VAPB. Our study brings further evidences of the VAPB role in ALS as a diagnostic biomarker. View Full-Text
Keywords: ALS; biomarker; VAPB ER-aggregates; endoplasmic reticulum; flow cytometry; PBMC; immunofluorescence ALS; biomarker; VAPB ER-aggregates; endoplasmic reticulum; flow cytometry; PBMC; immunofluorescence
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Cadoni, M.P.L.; Biggio, M.L.; Arru, G.; Secchi, G.; Orrù, N.; Clemente, M.G.; Sechi, G.; Yamoah, A.; Tripathi, P.; Orrù, S.; Manetti, R.; Galleri, G. VAPB ER-Aggregates, A Possible New Biomarker in ALS Pathology. Cells 2020, 9, 164.

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