Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Osteoprotegerin system and coronary atherosclerotic heart disease:an update / 天津医药

Osteoprotegerin (OPG), as a member of the tumor necrosis factor (TNF) superfamily, is a soluble secretary glycoprotein, which is accompanied with NF-κB receptor activator (RANK), NF-κB receptor activator ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to form osteoprotegerin system. A large number of clinical and experimental studies have confirmed that osteoprotegerin system participates in physiological processes such as endothelial function, inflammatory reaction, oxidative stress and apoptosis, which is expected to be a biomarker for the occurrence, development, severity and long-term prognosis of coronary heart disease. In this paper, we summarized the biological effects and mechanism of the osteoprotegerin system in the occurrence and development of coronary heart disease and its future clinical application.