Taliglucerase Alfa Reduces Amyloid-β Burden by Restoring Autophagic Pathways in a Neuronal Model of Alzheimer’s Disease

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Özkurt Ç., KÖSE S., KARASU Ç., KORTHOLT A., Kelicen-Uğur P.

Neurochemical Research, vol.51, no.3, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 51 Issue: 3
  • Publication Date: 2026
  • Doi Number: 10.1007/s11064-026-04792-w
  • Journal Name: Neurochemical Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
  • Keywords: Alzheimer’s disease, Autophagy, Enzyme replacement therapy, Lysosomal storage disorder, Taliglucerase alfa, β-Glucocerebrosidase
  • Open Archive Collection: AVESIS Open Access Collection
  • Gazi University Affiliated: Yes

Abstract

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.