Studies On Pharmacological Mechanism Of Marine Sulfated Oligosaccharide HSH-971 On Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia, progressive cognitive deficits being the primary symptom. AD is neuropathologically characterized by amyloid and neurofibrillary tangle depositions, basal forebrain cholinergic deficit, and extensive neuronal loss and synaptic changes in the cortex and hippocampus. The formation, metabolism and toxicity of Aβ play an important role in AD pathophysiology, it may cause neuronal loss via a number of possible mechanisms, including Ca²⁺ homeostasis disturbance, oxidative stress, excitotoxicity, mitochondria dysfunction, energy depletion, apoptosis, neuro-inflammation. The inhibition of Aβ toxicity is the main goal of AD treatment.HSH-971 is marine-derived sulfated oligosaccharide of low molecular weight, which has special binding site with Aβ and can inhibit the aggregation of Ap. The aim of of this study was to determine the anti-demential effect of HSH-971 based on AP-injected mice model and D-galactose-induced aging mice model. The newly developed microarray was introduced in the study to explore the molecular mechanism of protection effect of HSH-971 on Ap mice model. And further studies were carried out to observe the protective effect of HSH-971 on PC12 cells or cultured primary cortical neurons injured by AP25-35 or D-galactose.Part â…  Studies on the protective effect of HSH-971 in cultured PC12 cells and mice model injured by Aβ1. HSH-971 at the concentration of 1,10,100μg/ml could inhibit the aggregation of Aβ_1-40 in vitro by congo red bining and electron microscopy at 24 h and 48 h; HSH-971 also could inhibit the binding of Aβ_25-35 and thioflavin T, the percentage of binding would be less than 20% when concentration of HSH-971...