ROLE OF TAU IN NEURODEGENERATION: POTENTIAL MECHANISMS AND THERAPEUTICS

Abstract

Tauopathies are neurodegenerative diseases that are characterized by the presence of hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain and included Alzheimer’s disease and frontotemporal dementia. Epidemiology studies have shown the link between type-2 diabetes (T2DM) and AD. T2DM is characterized by hyperglycemia and insulin resistance. Previously, high glucose levels have been shown to induce tau phosphorylation but its effects on AD-specific tau phosphorylation remains to be investigated. The first study will address the effects of high glucose on AD-specific tau phosphorylation and its mechanism in SH-SY5Y which overexpress tau441. NFTs is known to correlate with cognitive impairment, suggesting that targeting tau phosphorylation may be therapeutic effective. Several components of MLC901 have been shown to have effect on tau phosphorylation, but it remains unknown whether MLC901n itself has the same effect. The will be investigated in the second study to assess the effects of MLC901 on AD-specific tau phosphorylation.