Heparan-sulfate proteoglycans found to influence Alzheimer's cell pathology

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMJul 5 2024 In a recent study published in IScience, a team of researchers from the United States examined the impact of heparan-sulfate-modified proteoglycans on Alzheimer's disease-associated pathways in mitochondrial function, autophagy, and liposomes using mouse astrocytes and human cells.

Most of the pharmaceutical strategies for developing Alzheimer's disease treatments have focused on these histopathological abnormalities, especially amyloid plaques, and some have been successful in slowing cognitive loss. They also investigated whether modulating HSPG-mediated signalling impacted these processes in fruit flies or Drosophila, which countered the deficits of a mutated PSEN1 gene.

HSPGs are found abundantly in the extracellular matrix and the cell surface and are binding sites to various growth factors, proteins, and growth factor receptors. They are also vital in signaling complex assembly and regulating fibroblast growth factor and other proteins involved in exocytosis and endocytosis.

They also investigated the genes associated with the major processes, such as lipid metabolism, autophagy, and mitochondrial function, affected by Alzheimer's disease. Furthermore, the loss-of-function mutations that lowered heparan-sulfate function increased autophagy and mitochondrial function and decreased the formation of intracellular lipid droplets. These results showed that lowering HSPG function alleviated the processes implicated in Alzheimer's disease.

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