Akademik Veri Yönetim Sistemi
Neurochemical Research, cilt.51, sa.3, 2026 (SCI-Expanded, Scopus)
Intraneuronal amyloid-beta (Aβ) accumulation and autophagic dysfunction are key pathological features of Alzheimer’s disease (AD). Mutations in GBA1, which encodes the lysosomal enzyme β-glucocerebrosidase (GCase), are linked to several neurodegenerative disorders, but the role of GCase in AD remains incompletely understood. In this exploratory, proof-of-concept study, we investigated whether taliglucerase alfa (TAL), a recombinant human GCase, may influence intracellular Aβ accumulation by modulating autophagy pathways in a neuronal AD model. Endogenous Aβ accumulation was induced in mouse hippocampal neuronal cells (HT-22) by exposure to low-molecular-weight Aβ1−42 oligomer-enriched assemblies (oAβ1−42), followed by treatment with TAL. Soluble Aβ levels and selected components of the autophagy–lysosome pathway, including GCase, cathepsin B, p62/sequestosome-1 (p62/SQSTM1), and mammalian target of rapamycin (mTOR), were evaluated using Western blotting, ELISA, and RT-PCR. In this in vitro model, TAL treatment was associated with a reduction in intracellular monomeric Aβ levels. This observation was accompanied by changes in mTOR signaling and p62 levels, suggestive of modulation of autophagy-related processes. Overall, these results provide preliminary, hypothesis-generating evidence supporting a potential association between lysosomal GCase augmentation and Aβ-related and autophagy-associated processes in AD. Further studies, including expanded experimental validation and in vivo investigations, are required to clarify the underlying mechanisms and translational relevance.