Cypin: A novel target for traumatic brain injury.

Cypin: A novel target for traumatic brain injury.
Neurobiol Dis. 2018 Jul 18;:
Authors: Swiatkowski P, Sewell E, Sweet ES, Dickson S, Swanson RA, McEwan SA, Cuccolo N, McDonnell ME, Patel MV, Varghese N, Morrison B, Reitz AB, Meaney DF, Firestein BL
Abstract
Cytosolic PSD-95 interactor (cypin), the primary guanine deaminase in the brain, plays key roles in shaping neuronal circuits and regulating neuronal survival. Despite this pervasive role in neuronal function, the ability for cypin activity to affect recovery from acute brain injury is unknown. A key barrier in identifying the role of cypin in neurological recovery is the absence of pharmacological tools to manipulate cypin activity in vivo. Here, we use a small molecule screen to identify two activators and one inhibitor of cypin's guanine deaminase activity. The primary screen identified compounds that change the initial rate of guanine deamination using a colorimetric assay, and secondary screens included the ability of the compounds to protect neurons from NMDA-induced injury and NMDA-induced decreases in frequency and amplitude of miniature excitatory postsynaptic currents. Hippocampal neurons pretreated with activators preserved electrophysiological function and survival after NMDA-induced injury in vitro, while pretreatment with the inhibitor did not. The effects of the activators were abolished when cypin was knocked down. Administering either cypin activator directly int...

Source: Neurobiology of Disease - July 18, 2018 Category: Neurology Authors: Swiatkowski P, Sewell E, Sweet ES, Dickson S, Swanson RA, McEwan SA, Cuccolo N, McDonnell ME, Patel MV, Varghese N, Morrison B, Reitz AB, Meaney DF, Firestein BL Tags: Neurobiol Dis Source Type: research