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Its main pathological hallmark is the accumulation of \u03b1\u2010synuclein in oligodendrocytes, leading to glial and neuronal dysfunction and neurodegeneration. These features are recapitulated in the PLP\u2010h\u03b1Syn mouse model expressing human \u03b1\u2010synuclein in oligodendrocytes. At present, there is no effective disease\u2010modifying therapy. Previous experiments have shown that the aggregation inhibitor, anle138b, reduces neurodegeneration and behavioral deficits in mouse models of other proteinopathies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To test the therapeutic potential of anle138b in a mouse model of MSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two\u2010month\u2010old PLP\u2010h\u03b1Syn mice were fed over a period of 4 months with pellets containing anle138b at two different doses (0.6 and 2 g\/kg) and compared to healthy controls and PLP\u2010h\u03b1Syn mice fed with placebo pellets. At the end of the treatment, behavioral and histological analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed a reversal of motor function to healthy control levels when PLP\u2010h\u03b1Syn mice were treated with both doses of anle138b. Histological and molecular analyses showed a significant reduction in \u03b1\u2010synuclein oligomers and glial cytoplasmic inclusions in animals fed with anle138b compared to nontreated mice. These animals also present preservation of dopaminergic neurons and reduction in microglial activation in SN correlating with the \u03b1\u2010synuclein reduction observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Anle138b reduces \u03b1\u2010synuclein accumulation in PLP\u2010h\u03b1Syn mice, leading to neuroprotection, reduction of microglial activation, and preservation of motor function supporting the use of anle138b in a future clinical trial for MSA. \u00a9 2018 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  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