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Full-Text Articles in Medicine and Health Sciences
Characterization And Treatment Of A Novel Mouse Model Of Tsc-Associated Autism, Rachel Michelle Reith
Characterization And Treatment Of A Novel Mouse Model Of Tsc-Associated Autism, Rachel Michelle Reith
Dissertations & Theses (Open Access)
Tuberous sclerosis complex (TSC) is a dominant tumor suppressor disorder caused by mutations in either TSC1 or TSC2. The proteins of these genes form a complex to inhibit the mammalian target of rapamycin complex 1 (mTORC1), which controls protein translation and cell growth. TSC causes substantial neuropathology, often leading to autism spectrum disorders (ASDs) in up to 60% of patients. The anatomic and neurophysiologic links between these two disorders are not well understood. However, both disorders share cerebellar abnormalities. Therefore, we have characterized a novel mouse model in which the Tsc2 gene was selectively deleted from cerebellar Purkinje cells (Tsc2f/-;Cre). …
The Regulation Of Mtorc2 Kinase Activity And Complex Integrity, Chien-Hung Chen
The Regulation Of Mtorc2 Kinase Activity And Complex Integrity, Chien-Hung Chen
Dissertations & Theses (Open Access)
Growth factor signaling promotes anabolic processes via activation of the
PI3K-Akt kinase cascade. Deregulation of the growth factor-dependent PI3K-Akt
pathway was implicated in tumorigenesis. Akt is an essential serine/threonine
protein kinase that controls multiple physiological functions such as cell growth,
proliferation, and survival to maintain cellular homeostasis. Recently, the
mammalian Target of Rapamycin Complex 2 (mTORC2) was identified as the
main Akt Ser-473 kinase, and Ser-473 phosphorylation is required for Akt
hyperactivation. However, the detailed mechanism of mTORC2 regulation in
response to growth factor stimulation or cellular stresses is not well understood.
In the first project, we studied the regulation …