title: The role of AEG-1/MTDH/LYRIC in the pathogenesis of central nervous system disease.
abstract: Astrocyte-elevated gene-1 (AEG-1/MTDH/LYRIC) is a potent oncogene that regulates key cellular processes underlying disease of the central nervous system (CNS). From its involvement in human immunodeficiency virus (HIV)-1 infection to its role in neurodegenerative disease and malignant brain tumors, AEG-1/MTDH/LYRIC facilitates cellular survival and proliferation through the control of a multitude of molecular signaling cascades. AEG-1/MTDH/LYRIC induction by HIV-1 and TNF highlights its importance in viral infection, and its incorporation into viral vesicles supports its potential role in active viral replication. Overexpression of AEG-1/MTDH/LYRIC in the brains of Huntington's disease patients suggests its function in neurodegenerative disease, and its association with genetic polymorphisms in large genome-wide association studies of migraine patients suggests a possible role in the pathogenesis of migraine headaches. In the field of cancer, AEG-1/MTDH/LYRIC promotes angiogenesis, migration, invasion, and enhanced tumor metabolism through key oncogenic signaling cascades. In response to external stress cues and cellular mechanisms to inhibit further growth, AEG-1/MTDH/LYRIC activates pathways that bypass cell checkpoints and potentiates signals to enhance survival and tumorigenesis. As an oncogene that promotes aberrant cellular processes within the CNS, AEG-1/MTDH/LYRIC represents an important therapeutic target for the treatment of neurological disease.
authors.affiliation: Department of Neurology and Neuroscience, Weill-Cornell Medical Center-New York Presbyterian Hospital, New York, NY, USA. noch@temple.edu
authors.forename: Evan K
authors.initials: EK
authors.lastname: Noch
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D016601:RNA-Binding Proteins
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins
keywords: AEG-1/MTDH/LYRIC; CNS; Cancer; Glioblastoma; HIV
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