Combination Gene Delivery Reduces Spinal Cord Pathology in Rats With Peripheral Neuropathic Pain.

Although peripheral neuropathic pain is caused by peripheral nerve injury, it is not simply a peripheral nervous system disease. It causes abnormalities in both the central and peripheral nervous systems. Pathological phenomena, such as hyperactivation of sensory neurons and inflammation, are observed in both the dorsal root ganglion and spinal cord.

AAV-Mediated Combination Gene Therapy for Neuropathic Pain: GAD65, GDNF, and IL-10.

Neuropathic pain is a chronic pain state characterized by nerve damage, inflammation, and nociceptive neuron hyperactivity. As the underlying pathophysiology is complex, a more effective therapy for neuropathic pain would be one that targets multiple elements. Here, we generated recombinant adeno-associated viruses (AAVs) encoding three therapeutic genes, namely, , , and , with various combinations.

Ubiquitin specific protease 19 involved in transcriptional repression of retinoic acid receptor by stabilizing CORO2A.

Deubiquitination via deubiquitinating enzymes (DUBs) has been emerged as one of the important post-translational modifications, resulting in the regulation of numerous target proteins. In this study, we screened new protein biomarkers for adipogenesis, and related studies showed that ubiquitin specific protease 19 (USP19) as a DUB is gradually decreased during adipogenesis and it regulates coronin 2A (CORO2A) as one of the components for the nuclear receptor co-repressor (NCoR) complex in some studies. The regulation of CORO2A through the deubiquitinating activity of USP19 affected the transcriptional repression activity of the retinoic acid receptor (RAR), suggesting that USP19 may be involved in the regulation of RAR-mediated adipogenesis.

HAUSP-nucleolin interaction is regulated by p53-Mdm2 complex in response to DNA damage response.

HAUSP (herpes virus-associated ubiquitin specific protease, known as ubiquitin specific protease 7), one of DUBs, regulates the dynamics of the p53 and Mdm2 network in response to DNA damage by deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Its concerted action increases the level of functional p53 by preventing proteasome-dependent degradation of p53. However, the protein substrates that are targeted by HAUSP to mediate DNA damage responses in the context of the HAUSP-p53-Mdm2 complex are not fully identified.

Polyclonal and monoclonal antibodies specific for ubiquitin-specific protease 20.

Ubiquitination and deubiquitination are important processes for numerous intracellular mechanisms, and the imbalance of these two processes can cause severe diseases including cancer. Accordingly, deubiquitinating enzymes (DUBs) responsible for deubiquitination from their protein substrates become attractive targets for many studies. USP20, also known as VDU2, belongs to ubiquitin-specific protease (USP) subfamily of DUBs and has several important roles in cells as shown with other DUBs.