1. @entity6602 ( @entity6602 ) is an inherited @entity209 predominantly characterized by @entity51 and cerebral atrophy whose patophysiology is poorly known. 2. We investigated here whether the branched-chain @entity1522 (BCAA) @entity368 (Leu), @entity6778 (Ile) and @entity4857 ( @entity2596 ), which are the biochemical hallmark of this disorder, could alter astrocyte morphology and cytoskeleton reorganization by exposing cultured astrocytes from cerebral cortex of neonatal @entity35 to various concentrations of the @entity1522 . A change of cell morphology from the usual polygonal to the appearance of fusiform or process-bearing cells was caused by the BCAA. Cell death was also observed when astrocytes were incubated in the presence of BCAA for longer periods. 3. @entity2596 -treated astrocytes presented the most dramatic morphological alterations. Immunocytochemistry with anti-actin and anti- @entity40 antibodies revealed that all BCAA induced reorganization of actin and @entity40 cytoskeleton. In addition, @entity4990 , an activator of RhoA GTPase pathway, was able to totally prevent the morphological alterations and cytoskeletal reorganization induced by @entity2596 , indicating that the RhoA signaling pathway was involved in these effects. 4. Furthermore, @entity908 attenuated the morphological alterations provoked by the BCAA, the protection being more pronounced for @entity2596 , suggesting that impairment of energy homeostasis is partially involved in BCAA cytotoxic action. The data indicate that the BCAA accumulating in @entity6602 are toxic to astrocyte cells, a fact that may be related to the pathogenesis of the @entity51 of @entity6602 @entity1 .

Morphological alterations and cell death provoked by the branched-chain alpha-amino acids accumulating in XXXX in astrocytes from @entity35 cerebral cortex.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity4990 :: ('MESH:C032881', 'Chemical') :: ['lysophosphatidic acid'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity368 :: ('CHEBI:25017', 'Chemical') :: ['leucine'] @entity2596 :: ('CHEBI:16414', 'Chemical') :: ['Val'] @entity908 :: ('MESH:D003401', 'Chemical') :: ['creatine'] @entity51 :: ('MESH:D009461', 'Disease') :: ['neurological dysfunction'] @entity6778 :: ('CHEBI:24898', 'Chemical') :: ['isoleucine'] @entity40 :: ('24387(Tax:10116)', 'Gene') :: ['GFAP'] @entity4857 :: ('CHEBI:27266', 'Chemical') :: ['valine'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic disorder'] @entity6602 :: ('MESH:D008375', 'Disease') :: ['Maple syrup urine disease', 'MSUD']
@entity6602 :: (MESH:D008375,Disease) :: ['maple syrup urine disease']
