The relationships between senile plaques, neurofibrillary tangles and sulfated polysaccharides / 中国药理学通报

ABSTRACT

Two aberrant structures, extracellular senile plaques (SP) and intracellular neurofibrillary tangles (NFTs) are the characteristic neuropathological hallmarks of Alzheimers disease (AD). Amyloid ? protein (A?) and hyperphosphorylated tau protein are the major components of SP and NFTs respectively. A large body of evidence has highlighted the pivotal role of sulfated polysaccharides in the amyloidogenesis and formation of NFTs. The underlying mechanisms of the involvement of sulfated polysaccharides in the development of AD were reported to contribute to their high affinity for both A? and tau protein. Sulfated polysaccharides not only promoted the ? secretase cleavage of APP and the increased production of A? and induced the aggregation and deposition of A?, but also facilitated the phosphylation of tau and promoted tau polymerization into fibrils and tangle formation. On the other hand, the neurotrophic effects exerted by sulfated polysaccharides were also demonstrated. These notions were probably due to the inhibition of the formation of A? fibrils or to the counteraction of the abnormal phosphorylation of tau by promoting the protein phosphatase2B activity, which has been speculated to be attributed to the variation in either structural backbone or degree of sulfation or position of sulfation. Putting together, the appropriate structural modification of sulfated polysaccharides may be effective as therapeutic agents for AD.