{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:21:47Z","timestamp":1792120907905,"version":"4.4.0"},"reference-count":85,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science, Technology &amp; Innovation Funding Authority (STDF)","award":["45960"],"award-info":[{"award-number":["45960"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disease that badly impacts patients and their caregivers. AD is characterized by deposition of amyloid beta (A\u03b2) and phosphorylated tau protein (pTau) in the brain with underlying neuroinflammation. We aimed to develop a neuroprotective paradigm by loading verapamil (VRH) into hyaluronic acid-modified carbon quantum dots (CQDs) and comparing its effectiveness with the free form in an AD-like model in rats induced by lipopolysaccharide (LPS). The experimental rats were divided into seven groups: control, LPS, CQDs, early free VRH (FVRH), late FVRH, early verapamil carbon quantum dots (VCQDs), and late VCQDs. Characterizations of VCQDs, the behavioral performance of the rats, histopathological and immunohistochemical changes, some AD hallmarks, oxidative stress biomarkers, neuro-affecting genes, and DNA fragmentation were determined. VRH was successfully loaded into CQDs, which was confirmed by the measured parameters. VRH showed enhancement in cognitive functions, disruption to the architecture of the brain, decreased A\u03b2 and pTau, increased antioxidant capacity, modifiable expression of genes, and a decline in DNA fragmentation. The loaded therapy was superior to the free drug. Moreover, the early intervention was better than the late, confirming the implication of the detected molecular targets in the development of AD. VRH showed multifaceted mechanisms in combating LPS-induced neurotoxicity through its anti-inflammatory and antioxidant properties, thereby mitigating the hallmarks of AD. Additionally, the synthesized nanosystem approach exhibited superior neuroprotection owing to the advantages offered by CQDs. However, finding new actionable biomarkers and molecular targets is of decisive importance to improve the outcomes for patients with AD.<\/jats:p>","DOI":"10.3390\/ijms25147790","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T16:35:58Z","timestamp":1721234158000},"page":"7790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mechanistic Insights of Neuroprotective Efficacy of Verapamil-Loaded Carbon Quantum Dots against LPS-Induced Neurotoxicity in Rats"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-4125","authenticated-orcid":false,"given":"Esraa M.","family":"Mosalam","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya Ibrahim","family":"Elberri","sequence":"additional","affiliation":[{"name":"Genetic Engineering and Molecular Biology Division, Department of Zoology, Faculty of Science, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-1792","authenticated-orcid":false,"given":"Mahmoud S.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Department, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Monufia, Egypt"},{"name":"Department of Pharm D, Faculty of Pharmacy, Jadara University, Irbid 21110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-9267","authenticated-orcid":false,"given":"Hend Mohamed","family":"Abdel-Bar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, University of Sadat City (USC), Sadat City 32897, Monufia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5304-2747","authenticated-orcid":false,"given":"Abdel-Aziz A.","family":"Zidan","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Damanhur University, Damanhur 22511, Beheira, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-4290","authenticated-orcid":false,"given":"Hany A.","family":"Batakoushy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-4675","authenticated-orcid":false,"given":"Hend E.","family":"Abo Mansour","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy, Menoufia University, Shebin El-Kom 32511, Menoufia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Skrzypczak-Wiercioch, A., and Sa\u0142at, K. 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