Taliglucerase alfa reduces intracellular Aβ burden by restoring autophagy in neuronal Alzheimer's model

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline, with no disease-modifying treatments available. Key pathological hallmarks include intraneuronal accumulation of amyloid-beta (Aβ) and significant autophagic dysfunction. Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are strongly linked to various neurodegenerative conditions, yet its precise role in AD pathogenesis and Aβ clearance remains incompletely understood. Current therapies primarily manage symptoms, highlighting an urgent need for interventions targeting underlying mechanisms like lysosomal and autophagic pathways.

This exploratory in vitro study investigated taliglucerase alfa, a recombinant human GCase, on intracellular Aβ accumulation and autophagy. Mouse hippocampal neuronal cells (HT-22) were used as an AD model. Endogenous Aβ accumulation was induced by exposing cells to low-molecular-weight Aβ1-42 oligomer-enriched assemblies (oAβ1-42). Cells were then treated with taliglucerase alfa. Soluble Aβ levels and key autophagy-lysosome pathway components, including GCase, cathepsin B, p62/SQSTM1, and mTOR, were evaluated using Western blotting, ELISA, and RT-PCR.