RESUMO
Glioblastoma multiforme (GBM) is the most frequently occurring and devastating human brain malignancy, retaining almost universal mortality and a median survival of only 14 months, even with recent advances in multimodal treatments. Gliomas are characterised as being both highly resistant to chemo- and radiotherapy and highly invasive, rendering conventional interventions palliative. The continual dismal prognosis for GBM patients identifies an urgent need for the evolutionary development of new treatment modalities. This includes molecular targeted therapies as many signaling molecules and associated pathways have been implicated in the development and survival of malignant gliomas including the protein kinase, glycogen synthase kinase 3 beta (GSK-3ß). Here we review the activity and function of GSK-3ß in a number of signaling pathways and its role in gliomagenesis.
Assuntos
Neoplasias Encefálicas/enzimologia , Glioblastoma/enzimologia , Quinase 3 da Glicogênio Sintase/fisiologia , Animais , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Glioblastoma/patologia , Quinase 3 da Glicogênio Sintase/química , Glicogênio Sintase Quinase 3 beta , Humanos , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Transdução de Sinais/fisiologiaRESUMO
A new haemoglobin variant with a decreased oxygen affinity is described, in which the substitution, alpha 94 (G1) Asp replaced by Asn, affects the alpha1beta2 contact alpha1G1-beta2G4. The relevance of this variant to our understanding of the importance of the hydrogen bond between alpha1G1 and beta2G4 in Perutz's model of oxyhaemoglobin A is discussed.
