en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Alzheimer&rsquo;s disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-beta (A&beta;) accumulation, leading to inflammation, oxidative stress, and impaired synaptic function. This study aimed to investigate the neuroprotective mechanisms of Vitis vinifera L. flavones (VTF) against A&beta;-induced neurodegeneration and their potential as AD therapeutics.<br> <strong>Methods</strong>: In an in vitro analysis, A&beta;1-42 oligomers were used to induce mitophagy in SH-SY5Y neuroblastoma cells. Cells were treated with VTF alone and in combination with chloroquine (CQ), a lysosomal inhibitor, to assess A&beta;1-42-induced mitophagy. Transmission electron microscopy (TEM) and immunofluorescence (IFC) were used to investigate the effects of A&beta;1-42 on autophagosomes and deposition. Cellular protection against A&beta;-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.<br> <strong>Results</strong>: CQ and VTF demonstrated significant neuroprotection against A&beta;1-42-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 A&beta; 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&ndash;lysosomal suppression. VTF+CQ maintained LC3-II/LC3-I balance, confirming VTF&rsquo;s role in preserving autophagy (P<0.01).<br> <strong>Conclusion</strong>: 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&rsquo;s neuroprotective efficacy.</div> <span style="font-size:12pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""><b><span style="background:white"><span style="color:black"></span></span></b></span></span></span> Alzheimer’s disease, Vitis vinifera L. flavones (VTF), Chloroquine (CQ), Amyloid-beta (Aβ)1-42-Aβ1-42-induced neurodegeneration, Mitophagy, Neuroprotective efficacy 641 656 http://bcn.iums.ac.ir/browse.php?a_code=A-10-6592-1&slc_lang=en&sid=1 Peng Zhang zhangp0115@126.com 13700319475328460054321 13700319475328460054321 No College of Public Health, Xinjiang Medical University, Urumqi, China. Hui Xiao xh22842023@163.com 13700319475328460054322 13700319475328460054322 Yes College of Public Health, Xinjiang Medical University, Urumqi, China.