Introduction: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (Aβ) accumulation, leading to inflammation, oxidative stress, and impaired synaptic function. This study aimed to investigate the neuroprotective mechanisms of Methods: In an in vitro analysis, Aβ1-42 oligomers were used to induce mitophagy in SHSY5Y neuroblastoma cells. Cells were treated with VTF alone and in combination with chloroquine (CQ), a lysosomal inhibitor, to assess Aβ1-42-induced mitophagy. Transmission electron microscopy (TEM) and immunofluorescence (IFC) were used to investigate the effects of Aβ1-42 on autophagosomes and deposition. Cellular protection against Aβ-induced damage was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blotting (WB) was used to determine the expression of autophagy-lysosomal pathway proteins (Beclin-1, Atg7, p62, and BACE1) and the LC3-II/LC3-I ratio, which serves as a marker of autophagy. Results: CQ and VTF demonstrated significant neuroprotection against Aβ1-42-induced neurodegeneration (P<0.05). VTF, alone or with CQ, increased viable cell count (~1.2-fold; P<0.05), indicating reparative capabilities. TEM and IFC showed robust protection by VTF and CQ against Aβ protein deposition, as well as preservation of mitochondrial and autophagosomal structures. VTF and CQ treatments reduced Beclin-1, Atg7, and BACE1 levels, indicating the modulation of mitophagy and autophagy-lysosomal suppression. VTF+CQ maintained LC3-II/LC3-I balance, confirming VTF's role in preserving autophagy (P<0.01). Conclusion: This study reveals the novel neuroprotective role of VTF, emphasizing its potential as an AD therapeutic. Future research should extend investigations to in vivo models and clinical settings to enhance our understanding of VTF's neuroprotective efficacy.