Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations.

摘要: Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with demyelinating neuropathies. Overexpression of wild type (wt) PMP22 or inhibition proteasomal degradation lead to the formation aggresomes, intracellular ubiquitinated aggregates. Aggresome has now been observed two mutant PMP22s, Tr- and TrJ-PMP22 when proteasome is inhibited. The these aggresomes required intact microtubules involved recruitment chaperones, including Hsp40, Hsp70, alphaB-crystallin. Spontaneously formed aggregates were also Schwann cells homozygous TrJ mice. Significant upregulation both ubiquitin-proteasomal lysosomal pathways occurred affected nerves suggesting that present. Thus, presence appears be a common finding neuropathy models overexpression some point mutations known cause mice humans.