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Often, these disorders are associated with disease\u2010amplifying neuroinflammation, a feature shared by progressive forms of multiple sclerosis (PMS), another poorly treatable disorder of the CNS. We have previously generated two mouse lines carrying distinct mutations in the oligodendrocytic <jats:italic>PLP1<\/jats:italic> gene that have initially been identified in patients fulfilling clinical criteria for multiple sclerosis (MS). These mutations cause a loss of function of the gene product resulting in a histopathological and clinical phenotype common to both PMS and genetic CNS disorders, like hereditary spastic paraplegias. Importantly, neuroinflammation comprising adaptive immune reactions promotes disease progression in these <jats:italic>PLP1<\/jats:italic> mutant models, opening the possibility to improve disease outcome of the respective disorders by targeting\/modulating inflammation. We here show that PLX3397, a potent inhibitor of the CSF\u20101R and targeting innate immune cells, attenuates neuroinflammation in our models by reducing numbers of resident microglia and attenuating T\u2010lymphocyte recruitment in the CNS. This leads to an amelioration of demyelination, axonopathic features and neuron loss in the retinotectal system, also reflected by reduced thinning of the inner retinal composite layer in longitudinal studies using noninvasive optical coherence tomography. Our findings identify microglia as important promoters of neuroinflammation\u2010related neural damage and CSF\u20101R inhibition as a possible therapeutic strategy not only for PMS but also for inflammation\u2010related genetic diseases of the nervous system for which causal treatment options are presently lacking.<\/jats:p>","DOI":"10.1002\/glia.23539","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T15:17:42Z","timestamp":1545232662000},"page":"277-290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Targeting microglia attenuates neuroinflammation\u2010related neural damage in mice carrying human <i>PLP1<\/i> mutations"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7628-0163","authenticated-orcid":false,"given":"Janos","family":"Groh","sequence":"first","affiliation":[{"name":"Department of Neurology, Section of Developmental Neurobiology University Hospital Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Section of Developmental Neurobiology University Hospital Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Berve","sequence":"additional","affiliation":[{"name":"Department of Neurology, Section of Developmental Neurobiology University Hospital Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"West","sequence":"additional","affiliation":[{"name":"Plexxikon Inc.  Berkeley California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5463-5592","authenticated-orcid":false,"given":"Rudolf","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Neurology, Section of Developmental Neurobiology University Hospital Wuerzburg  Wuerzburg 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