Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

Clinical Application of a New Assessment Tool for Myelopathy Hand Using Virtual Reality.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To assess the effectiveness of a new assessment tool, myelopathy-hand functional evaluation system (MFES), in evaluating the hand dysfunction of patients with cervical myelopathy in the 10-second grip-and-release test (10 second G-R test). SUMMARY OF BACKGROUND DATA: Clumsy fingers movement is a common symptom of myelopathy patients. Evaluating the impaired hand function can provide a strong basis in assessing the severity of myelopathy. Currently, no objective and effective evaluation method is widely accepted in clinical practice. METHODS: MFES mainly consists of a pair of wise-gloves and a computer with software. One hundred and ninety-eight consecutive participants were asked to wear the wise-gloves and then perform 10 seconds G-R test. The movements of each finger were recorded by MFES and converted into waveforms. Relevant waveform parameters were measured and analyzed. The Japanese Orthopedics Association (JOA) scores of each patient were marked and the maximum spinal cord compression (MSCC) was measured on midsagittal T2-weighted magnetic resonance imaging (MRI). RESULTS: Myelopathy patients had a lower number of G-R cycles and a longer time per cycle than healthy subjects. There were significant differences in adduction and abduction time in patients with JOA scores greater than 6, but not in healthy subjects and patients with JOA scores less than 6. The waveforms of ulnar three fingers in myelopathy patients were lower and wider than those in healthy individuals. The average ratio value of wave height to wave width (a/b) could quantitatively reflect such differences of waveforms. According to receiver operating characteristic (ROC) curve analysis, the optimal threshold value of the normal average ratio was more than 1.92. The average a/b value was correlated with the JOA scores of the motor function in the upper extremities (r = 0.842). CONCLUSION: MFES appears to be an objective and quantitative assessment tool for patients with cervical myelopathy. LEVEL OF EVIDENCE: 3.