Heparan sulfate as molecular chaperons in tau pathology

AVILA, CESAR L.; CHANTEPIE, SANDRINE; MEDINA, LUCIANA; VERA, CECILIA

Conferencia; BSMB Spring Meeting, 3rd-4th April 2017; 2017

The pathologic lesions of Alzheimer?s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The abnormallyphosphorylated protein tau accumulates intracellularly as neurofibrillary tangles. The driving misfolding process of this protein is still unclear and molecular chaperons able to induceconformational changes associated to the pathological processes are under research. Heparan sulfates proteoglycans (HSPG) are highly anionic polysaccharides classically present at theextracellular matrix and at the cell surface of most mammal cells. Under pathological conditions, HS chains in HSPG undergo a variety of changes on their structures, sulfation levels, and tissue orcellular locations. Recently, we showed that HS colocalize with intracellular tau in cell models of AD-related tauopathy. We hypothesized that upon interaction with tau, HS chains can induceconformational changes in the protein resulting in its abnormal phosphorylation and aggregation. Currently we are studying the role of HS as molecular chaperons involved in the mechanismsleading to tau pathology. Conformational insight comforting this hypothesis will be discussed.