Developing a Tanshinone IIA Memetic by Targeting MIOS to Regulate mTORC1 and Autophagy in Glioblastoma.

Tanshinone IIA (T2A) is a bioactive compound that provides promise in the treatment of glioblastoma multiforme (GBM), with a range of molecular mechanisms including the inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy. Recently, T2A has been demonstrated to function through sestrin 2 (SESN) to inhibit mTORC1 activity, but its possible impact on autophagy through this pathway has not been investigated. Here, the model system and GBM cell lines were employed to investigate the cellular role of T2A in regulating SESN to inhibit mTORC1 and activate autophagy through a GATOR2 component MIOS.

Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth.

Glioblastomas are a highly aggressive cancer type which respond poorly to current pharmaceutical treatments, thus novel therapeutic approaches need to be investigated. One such approach involves the use of the bioactive natural product Tanshinone IIA (T2A) derived from the Chinese herb Danshen, where mechanistic insight for this anti-cancer agent is needed to validate its use. Here, we employ a tractable model system, Dictyostelium discoideum, to provide this insight.

Gamma secretase orthologs are required for lysosomal activity and autophagic degradation in , independent of PSEN (presenilin) proteolytic function.

Mutations in the γ-secretase complex are strongly associated with familial Alzheimer disease. Both proteolytic and non-proteolytic functions for the γ-secretase complex have been previously described in mammalian model organisms, but their relative contributions to disease pathology remain unclear. Here, we dissect the roles of orthologs of the γ-secretase components in the model system , focusing on endocytosis, lysosomal activity and autophagy.

Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation.

Background: Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia.

Methods: We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice.

The neuroplastins: multifunctional neuronal adhesion molecules--involvement in behaviour and disease.

The neuroplastins np65 and np55 are neuronal and synapse-enriched immunoglobulin (Ig) superfamily cell adhesion molecules that contain 3 and 2 Ig domains, respectively. Np65 is neuron specific whereas np55 is expressed in many tissues. They are multifunctional proteins whose physiological roles are defined by the partner proteins they bind to and the signalling pathways they activate.