{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T03:28:06Z","timestamp":1785382086456,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2023-00208567"],"award-info":[{"award-number":["RS-2023-00208567"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the potential neuroprotective mechanisms of porcine brain enzyme hydrolysate (PBEH) against Alzheimer\u2019s disease pathology using differentiated SH-SY5Y cells. Differentiated neuronal cells were treated with 40 \u03bcM amyloid-\u03b2(1-42; A\u03b2) to induce neurotoxicity, followed by PBEH treatment (12.5\u2013400 \u03bcg\/mL), Com-A (peptide-based neuroprotective supplement; 200 \u03bcg\/mL) treatment, and Com-B (herbal extract known for improving memory function; 100 \u03bcg\/mL) treatment. Key assessments included cell viability, A\u03b2 aggregation in adding 10 \u03bcM A\u03b2, amyloidogenic proteins (APP, BACE), synaptic markers (BDNF, ERK), apoptotic markers (BAX\/BCL-2, caspase-3), oxidative stress (reactive oxygen species (ROS)), cholinergic function (ChAT, AChE), MAPK signaling (JNK, p38), and neuroinflammation (IL-1\u03b2). PBEH contained high concentrations of amino acids, including L-lysine (32.3 mg\/g), L-leucine (42.4 mg\/g), L-phenylalanine (30.0 mg\/g) and the PSIS peptide (86.9 \u03bcg\/g). Treatment up to 400 \u03bcg\/mL showed no cytotoxicity and had cognitive protection effects up to 152% under A\u03b2 stress (p &lt; 0.05). PBEH significantly attenuated A\u03b2 aggregation, decreased APP (28%) and BACE (51%) expression, enhanced synaptic function through increased BDNF, and restored ERK phosphorylation (p &lt; 0.05). Anti-apoptotic effects included a 76% reduction in the BAX\/BCL-2 ratio, a 47% decrease in caspase-3, and a 56% reduction in ROS levels. Cholinergic function showed restoration via increased ChAT activity (p &lt; 0.01) and decreased AChE activity (p &lt; 0.05). PBEH reduced IL-1\u03b2 levels by 70% and suppressed JNK\/p38 phosphorylation (p &lt; 0.05). While Com-A enhanced BDNF and Com-B showed anti-inflammatory effects, PBEH demonstrated activity across multiple pathway markers. In conclusion, these findings suggest that PBEH may enable neuronal preservation through multi-pathway modulation, establishing foundational evidence for further mechanistic investigation in cognitive enhancement applications.<\/jats:p>","DOI":"10.3390\/ijms26136030","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T06:49:38Z","timestamp":1750747778000},"page":"6030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective Mechanisms of Porcine Brain Enzyme Hydrolysate in Memory Impairment: Multi-Target Strategy Against Amyloid-\u03b2-Induced Neurotoxicity"],"prefix":"10.3390","volume":"26","author":[{"given":"Sun Myung","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of R&D, Unimed Pharmaceuticals Inc., Unimed Bldg., Seoul 05567, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of R&D, Unimed Pharmaceuticals Inc., Unimed Bldg., Seoul 05567, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of R&D, Unimed Pharmaceuticals Inc., Unimed Bldg., Seoul 05567, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Joon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of R&D, Unimed Pharmaceuticals Inc., Unimed Bldg., Seoul 05567, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Won","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of R&D, Unimed Pharmaceuticals Inc., Unimed Bldg., Seoul 05567, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Obesity\/Diabetes Research Center, Hoseo University, Asan-si 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ma, C., Hong, F., and Yang, S. 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