??Neuropatie ereditarie: i difetti del trasporto assonale come meccanismo chiave nello sviluppo della patologia

A progressive and length-dependent loss of peripheral nerve function characterizes peripheral inherited neuropathies. The main process at the base of the onset of these diseases is the axonal transport, directly or indirectly involved. One of the rarest inherited neuropathies is HSAN, a heterogeneous group of diseases characterized by peripheral nerve degeneration and a severe distal sensory loss. There are five types of HSAN, but I wanted to concentrate on HSAN type II. Some mutations were associated with HSAN II, as FAM134B and HSN2, but the etiology of the disease remains misunderstood. In few cases, mutations in KIF1A, an axonal transporter responsible for anterograde transport of TrkA, were found. TrkA, a high-affinity tyrosine kinase receptor, is involved in pain perception. At the beginning of the study, a homozygous mouse was generated, and, after some pain perception tests, it was clear that he detected pain less than the wild-type one. This mouse was lethal, thus, a heterozygous mouse was generated: after some analysis, scientists understood that also this mouse developed sensory neuropathy: indeed, there was a high level of apoptosis in Kif1a +/- DRG and the vesicle movements were altered. Also TRPV1, a cation channel whose phosphorylation is controlled by TrkA, had a different expression: in Kif1a +/- cells it was diminished on the cellular surface. However, the real innovation of the study is that the phosphorylation, due to PI3K pathway, can rescue the phenotype. This data can be useful for the future possibilities of therapy.