Tuberous Sclerosis

Study findings on tuberous sclerosis are outlined in reports from University of Amsterdam

Tuberous Sclerosis Library Library Home This article was published in Pain & Central Nervous System Week, which you can subscribe to online.

"Cytomegaly in developmental brain malformations may reflect in aberrant activation of the mTOR and beta-catenin signaling cascades, known regulators of cell size. We hypothesized that there is aberrant co-expression of phospho-ribosomal S6 (P-S6) protein, a downstream effector of the mTOR cascade, as well as cyclin D1, a downstream effector of the beta-catenin pathway, in BCs and cytomegalic neurons in HMEG. We hypothesized that mutations in PTEN (a cause of HMEG associated with Proteus syndrome), TSC1 or TSC2 (tuberous sclerosis complex) genes, which are known to modulate beta-catenin and mTOR signaling could cause sporadic HMEG. Expression of cyclin D1, phospho-p70 S6 kinase (P-p70S6K, another mTOR cascade kinase), P-S6, MAP2, NeuN, or GFAP was determined by immunohistochemistry in HMEG brain tissue (n=7 specimens). Cyclin D1, P-p70S6K, and P-S6 proteins were co-localized in BCs and CNs in the enlarged hemisphere but not in the unaffected hemisphere or in morphologically normal tissue. Cyclin D1 and P-S6 proteins were not detected in GFAP-labeled astrocytes. Sequencing of PTEN, TSC1, and TSC2 genes in cytomegalic cells co-expressing cyclin D1 and P-S6 proteins did not reveal mutations. Selective expression of cyclin D1 and P-S6 in cytomegalic cells in HMEG suggests co-activation of the beta-catenin and mTOR cascades," wrote E. Aronica and colleagues, University of Amsterdam.

The researchers concluded: "PTEN, TSC1, or TSC2 gene mutations were not detected suggesting that sporadic HMEG is distinct from HMEG associated with Proteus syndrome or tuberous sclerosis complex."

Aronica and colleagues published the results of their research in Acta Neuropathologica (Co-expression of cyclin D1 and phosphorylated ribosomal S6 proteins in hemimegalencephaly. Acta Neuropathologica, 2007;114(3):287-93).

For additional information, contact E. Aronica, University of Amsterdam, Dept. of (Neuro)Pathology, Academic Medical Center, Amsterdam, Netherlands.

The publisher of the journal Acta Neuropathologica can be contacted at: Springer, 233 Spring Street, New York, NY 10013, USA.

Keywords: Netherlands, Amsterdam, Central Nervous System Disease, Epilepsy, Genetics, Neurology, Proteus Syndrome, Tuberous Sclerosis.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.