Der Einfluss von Neuregulin-1 auf Erkrankungen des peripheren Nervensystems

摘要: A duplication of the gene encoding peripheral myelin protein 22kDa (PMP22) underlies commonest inherited neuropathy, Charcot Marie Tooth disease 1A (CMT1A). Although demyelination is a characteristic feature, clinical impairment CMT1A patients determined by extent axonal loss. Patients suffer from slowly progressive, distally pronounced muscle atrophy and sensory impairments. therapy not available yet. In present doctoral thesis it shown that, with help Pmp22 transgenic rodent models for CMT1A, overexpressing Schwann cells acquire persistent dedifferentiation phenotype already during early postnatal development which similar to cell after acute nerve injury. In contrast lesion, in triggered an imbalanced activity PI3K/AKT MEK/ERK signaling pathways. common feature both models, however, de novo expression Neuregulin-1 type I cells. With conditional knock-out mice without cells, demonstrated that injury essential proper regeneration. Also cell-Neuregulin-1 showed neuropathic phenotype. Vice versa, experimental reinforcement overexpression lead improvement various features mice. In preclinical therapeutic approach recombinant rats development, almost diminished impaired differentiation improved function until adulthood. These data suggest within limited time window crucial long-term support.