A new era for myelin research in Neurofibromatosis type 1.

ABSTRACT

Evidence for myelin regulating higher-order brain function and disease is rapidly accumulating; however, defining cellular/molecular mechanisms remains challenging partially due to the dynamic brain physiology involving deep changes during development, aging, and in response to learning and disease. Furthermore, as the etiology of most neurological conditions remains obscure, most research models focus on mimicking symptoms, which limits understanding of their molecular onset and progression. Studying diseases caused by single gene mutations represents an opportunity to understand brain dys/function, including those regulated by myelin. Here, we discuss known and potential repercussions of abnormal central myelin on the neuropathophysiology of Neurofibromatosis Type 1 (NF1). Most patients with this monogenic disease present with neurological symptoms diverse in kind, severity, and onset/decline, including learning disabilities, autism spectrum disorders, attention deficit and hyperactivity disorder, motor coordination issues, and increased risk for depression and dementia. Coincidentally, most NF1 patients show diverse white matter/myelin abnormalities. Although myelin-behavior links were proposed decades ago, no solid data can prove or refute this idea yet. A recent upsurge in myelin biology understanding and research/therapeutic tools provides opportunities to address this debate. As precision medicine moves forward, an integrative understanding of all cell types disrupted in neurological conditions becomes a priority. Hence, this review aims to serve as a bridge between fundamental cellular/molecular myelin biology and clinical research in NF1.