{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:20:23Z","timestamp":1766035223521,"version":"3.48.0"},"reference-count":65,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["114WFP2510250"],"award-info":[{"award-number":["114WFP2510250"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neurodegenerative diseases (NDs) have emerged as a significant global health crisis, disproportionately affecting the aging population. As longevity increases, the incidence, healthcare costs, and caregiver burden associated with NDs are escalating at an alarming rate. As of recent data, NDs such as Alzheimer\u2019s disease (AD) are not only significant health burdens but also reflect a complex interplay between socio-economic factors and healthcare systems worldwide. Gac fruit (Momordica cochinchinensis) is a rich source of bioactive compounds that has been used as food and traditional medicine. Gac fruit ameliorates memory deficits, enhances beta amyloid (A\u03b2)1\u201342 clearance, and induces neurite outgrowth. In this study, we examined the anti-neurodegenerative and synaptic improvement effect of fresh gac fruit parts extracts (FGPEs) produced from different solvents. Results showed that the 80% ethanol extract of peel (PE-EtOH) and ethyl acetate extract of seed (SE-EtOAc) significantly protected HT-22 cells by attenuating A\u03b2-induced cell death, intracellular reactive oxygen species (ROS) production, mitochondrial dysfunction, and synaptic dysfunction. PE-EtOH protected synaptic functions by significantly increasing the postsynaptic density protein-95 (PSD-95) and reducing the neurexin 2 mRNA expression. In contrast, SE-EtOAc increased the PSD-95 and neurexin 3 and reduced the neurexin 2 expressions. These findings indicate that PE-EtOH and SE-EtOAc could have great potential in ameliorating A\u03b2-induced toxicity in an HT-22 cell model.<\/jats:p>","DOI":"10.3390\/molecules30244767","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T15:15:08Z","timestamp":1765811708000},"page":"4767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effect of Fresh Gac Fruit Parts Against \u03b2-Amyloid-Induced Toxicity and Its Influence on Synaptic Gene Expression in HT-22 Cell Model"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-1438","authenticated-orcid":false,"given":"Asif","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4553-3727","authenticated-orcid":false,"given":"Chih-Li","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-7847","authenticated-orcid":false,"given":"Chin-Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, August 07). 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