HMGA1 deficiency: a pathogenic link between tau pathology and insulin resistance.

ABSTRACT:

Background

Growing evidence links tau-related neurodegeneration with insulin resistance and type 2 diabetes (T2D), though the underlying mechanisms remain unclear. Our previous research identified HMGA1 as crucial for insulin receptor (INSR) expression, with defects in the HMGA1 gene associated with insulin resistance and T2D. Here, we explore HMGA1 deficiency as a potential contributor to tauopathies, such as Alzheimer's disease (AD), and its connection to insulin resistance.

Methods

Immunoblot analyses, protein-DNA interaction studies, ChIP-qPCR, and reporter gene assays were conducted in human and mouse neuronal cell models. Tau immunohistochemistry, behavioural studies, and brain glucose metabolism were analysed in Hmga1-knockout mice. Additionally, a case-control study

SUBMITTER: Mirabelli M 

PROVIDER: S-EPMC12019291 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature