Title |
Active immunization against alpha-synuclein ameliorates the degenerative pathology and prevents demyelination in a model of multiple system atrophy
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Published in |
Molecular Neurodegeneration, March 2015
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DOI | 10.1186/s13024-015-0008-9 |
Pubmed ID | |
Authors |
Markus Mandler, Elvira Valera, Edward Rockenstein, Michael Mante, Harald Weninger, Christina Patrick, Anthony Adame, Sabine Schmidhuber, Radmila Santic, Achim Schneeberger, Walter Schmidt, Frank Mattner, Eliezer Masliah |
Abstract |
Multiple system atrophy (MSA) is a neurodegenerative disease characterized by parkinsonism, ataxia and dysautonomia. Histopathologically, the hallmark of MSA is the abnormal accumulation of alpha-synuclein (α-syn) within oligodendroglial cells, leading to neuroinflammation, demyelination and neuronal death. Currently, there is no disease-modifying treatment for MSA. In this sense, we have previously shown that next-generation active vaccination technology with short peptides, AFFITOPEs®, was effective in two transgenic models of synucleinopathies at reducing behavioral deficits, α-syn accumulation and inflammation. In this manuscript, we used the most effective AFFITOPE® (AFF 1) for immunizing MBP-α-syn transgenic mice, a model of MSA that expresses α-syn in oligodendrocytes. Vaccination with AFF 1 resulted in the production of specific anti-α-syn antibodies that crossed into the central nervous system and recognized α-syn aggregates within glial cells. Active vaccination with AFF 1 resulted in decreased accumulation of α-syn, reduced demyelination in neocortex, striatum and corpus callosum, and reduced neurodegeneration. Clearance of α-syn involved activation of microglia and reduced spreading of α-syn to astroglial cells. This study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies. |
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Geographical breakdown
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 11 | 10% |
Other | 5 | 4% |
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Pharmacology, Toxicology and Pharmaceutical Science | 6 | 5% |
Other | 20 | 17% |
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