Neurofibromatosis type 1: Piecing the puzzle together

被引:37
作者
Feldkamp, MM
Gutmann, DH
Guha, A
机构
[1] Toronto Hosp, Toronto Western Div, Div Neurosurg, Toronto, ON M5T 2S8, Canada
[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada
[3] Univ Toronto, Toronto, ON, Canada
[4] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
[6] Ontario Canc Inst, Dept Surg Oncol, Toronto, ON M4X 1K9, Canada
[7] Toronto Hosp, Peripheral Nerve Unit, Toronto, ON M5T 2S8, Canada
关键词
D O I
10.1017/S0317167100033990
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Neurofibromatosis type 1 (NF1) was first described in 1882 and is characterized by a diverse spectrum of clinical manifestations, including neurofibromas, cafe au lait spots, and Lisch nodules, NF1 is also noted for the higher risk: of associated malignancies, making it the most common tumour-predisposing disease in humans. Transmitted in an autosomal dominant manner, the NF1 gene was cloned in 1990, and belongs to the family of tumour suppressor genes. Since then, there has been an explosion in our understanding of how the gene product, neurofibromin, functions in normal cellular physiology, and how its loss in NF1 relates to the wide spectrum of clinical findings, including NF1-associated tumours. Neurofibromin is a major negative regulator of a key signal transduction pathway in cells, the Ras pathway, which transmits mitogenic signals to the nucleus, Loss of neurofibromin leads to increased levels of activated Ras (bound to GTP), and thus increased downstream mitogenic signaling. Our understanding of nenrofibromin's role within cells has allowed for the development of pharmacological therapies which target the specific molecular abnormalities in NF1 rumours. These include the farnesyl transferase inhibitors, which inhibit the post-translational modification of Ras, and other agents which modulate Ras-mediated signaling pathways.
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页码:181 / 191
页数:11
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