The interaction of the sulfated GAG appear to be through basic residues of the interacting proteins like Aβ, supporting previous studies demonstrating the importance of the sulfate moeities of sGAG for the formation of amyloid fibrils. On the other hand, the binding of sGAG to Aβ has been found to decrease Aβ degradation.
In addition Aβ and tau aggregates associate to sGAG in vivo. Different sGAG also facilitate the assembly in vitro of tau. SGAG including heparan, keratan and chondroitin sulfates strongly favor Aβ polymerization in vitro. It has been proposed that some compounds like sulfated glycosaminoglycans (sGAG) could promote the aggregation of Aβ and tau, and it has been even suggested that in Alzheimer's disease sGAG may provide a common link for Aβ and tau polymerization. We like to emphasize the importance of testing on both types of pathology (amyloid and tau) the potential drugs to be used for AD treatment.Īlzheimer's disease is characterized by the presence of two histopathological hallmarks the senile plaques or extracellular deposits mainly composed of amyloid-β peptide (Aβ) and the neurofibrillary tangles or intraneuronal inclusions composed of hyperphosphorylated tau protein. We also found that 3-APS does not affect the binding of tau to microtubules but may prevent the formation of tau-actin aggregates. Our results indicate that 3-APS favours tau aggregation, in tau transfected non-neuronal cells, and in neuronal cells. In this work, we have tested the action of 3-APS on cell viability, microtubule network, actin organization and tau aggregation. However, little is known about the action of 3-APS on tau protein aggregation. One of them is 3-amino-1-propane sulfonic acid (Tramiprosate, 3-APS, Alzhemed™), that was developed as a sulfated glycosaminoglycan mimetic, that could interact with Aβ peptide, preventing its aggregation. Since Aβ aggregates are found in the pathological cases, several strategies are under way to develop drugs that interact with Aβ to reduce its assembly. Alzheimer's disease (AD) is characterized by the presence of two histopathological hallmarks the senile plaques, or extracellular deposits mainly composed of amyloid-β peptide (Aβ), and the neurofibrillary tangles, or intraneuronal inclusions composed of hyperphosphorylated tau protein.