Active Immunization Against Alpha-Synuclein Ameliorates the Degenerative Pathology and Prevents Demyelination in a Model of Multiple System Atrophy

Mol Neurodegener. 2015 Mar 19;10:10. doi: 10.1186/s13024-015-0008-9.

Abstract

Background: 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.

Results: 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.

Conclusions: This study further validates the efficacy of vaccination with AFFITOPEs® for ameliorating the neurodegenerative pathology in synucleinopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / prevention & control*
  • Disease Models, Animal
  • Mice, Transgenic
  • Microglia / cytology
  • Microglia / immunology
  • Multiple System Atrophy / immunology
  • Multiple System Atrophy / pathology*
  • Multiple System Atrophy / prevention & control*
  • Neurons / cytology
  • Neurons / immunology
  • Oligodendroglia / cytology
  • Oligodendroglia / immunology
  • Parkinsonian Disorders / immunology
  • Parkinsonian Disorders / pathology*
  • Vaccination / methods
  • alpha-Synuclein / immunology*

Substances

  • alpha-Synuclein