title: Molecular implications of skin lesions in tuberous sclerosis.
abstract: Tuberous sclerosis (TS), neurocutaneous disorder resulting from the mutation of 1 of 2 genes, TSC1 or TSC2, is often associated with the formation of hamartomatous lesions in various organ systems, including the skin. TS patients may present with hypomelanic macules, confetti-like spots, facial angiofibromas, ungual fibromas, shagreen patches, forehead plaques, and other dermatological signs. Some of these manifestations are pathognomic for TS and thus should be carefully evaluated when TS diagnosis is suspected. Little is known however on molecular links connecting disease pathogenesis and formation of such hamartomas. In the current review, we describe molecular pathways thought to be responsible for the development of the disease and show how their upregulation may affect the skin. Special attention is paid to protein kinase B (PKB/Akt), extracellular signal-regulated kinase, and mammalian target of rapamycin, which have recently been found to participate in the control of melanin biosynthesis through microphthalmia-associated transcription factor and tyrosinase transcription.
authors.affiliation: Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland. jjozwiak@atdv.com.pl
authors.forename: Jarosław
authors.initials: J
authors.lastname: Jóźwiak
authors.forename: Ryszard
authors.initials: R
authors.lastname: Galus
mesh_terms: D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases