In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
Impaired GABAergic and glutamatergic synaptic function and loss of interneurons in the amygdala, hippocampus, and cerebellum cause characteristic disease symptoms in a mouse model juvenile neuronal ceroid lipofuscinosis.
Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.
GDC-0810 is a novel, orally bioavailable SERD that exhibits robust pre-clinical activity in models of ER+ breast cancer, including models of tamoxifen resistance, and those that express the ERα mutations, ER.Y537S and ER.D538G.
Viral transduction and gene manipulation of adult human brain slices will be of great value allowing investigations including therapeutic screening, electrophysiological and structural studies of properties of human CNS circuitry.