Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms.
BACKGROUND
Giant axonal neuropathy (GAN) is a progressive hereditary disease that affects the peripheral and central nervous systems. It is characterized morphologically by aggregates of intermediate filaments in different tissues. Mutations have been reported in the gene that codes for gigaxonin. Nevertheless, the underlying molecular mechanism remains obscure.


METHODS
Cell lines from 4 GAN patients and 4 controls were analyzed by iTRAQ.


RESULTS
Among the dysregulated proteins were ribosomal protein L29, ribosomal protein L37, galectin-1, glia-derived nexin, and aminopeptidase N. Also, nuclear proteins linked to formin-binding proteins were found to be dysregulated. Although the major role of gigaxonin is reported to be degradation of cytoskeleton-associated proteins, the amount of 76 structural cytoskeletal proteins was unaltered.


CONCLUSIONS
Several of the dysregulated proteins play a role in cytoskeletal reorganization. Based on these findings, we speculate that disturbed cytoskeletal regulation is responsible for formation of aggregates of intermediate filaments.
Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium.
Silke
S
Mussche
Boel
B
De Paepe
Joél
J
Smet
Katrien
K
Devreese
Willy
W
Lissens
Vedrana Milic
VM
Rasic
Matthew
M
Murnane
Bart
B
Devreese
Rudy
R
Van Coster
D001369:Axons / Q000378:metabolism*; D018826:CD13 Antigens / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D037483:Galectin 1 / Q000378:metabolism; D056768:Giant Axonal Neuropathy / Q000378:metabolism*; D006801:Humans; D008297:Male; D040901:Proteomics; D012269:Ribosomal Proteins / Q000378:metabolism; D058258:Serpin E2 / Q000378:metabolism
D037483:Galectin 1; C488984:RPL37 protein, human; D012269:Ribosomal Proteins; D058258:Serpin E2; C035078:ribosomal protein L29; D018826:CD13 Antigens