Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model
Abstract Alzheimer’s disease (AD) is responsible for more than 80% of cases of dementia in senior individuals globally. In the current study, the role of modulation of the FGF1/PI3K/Akt pathway in the protective effect of tozasertib was evaluated. Experimental dementia was induced in mice by injecti...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-13920-5 |
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| author | Darshpreet Kaur Amarjot Kaur Grewal Suad Hamdan Almasoudi Ahmad H Almehmadi Bshra A. Alsfouk Amit Kumar Varinder Singh Athanasios Alexiou Marios Papadakis Nermeen N. Welson Thakur Gurjeet Singh Gaber El-Saber Batiha |
| author_facet | Darshpreet Kaur Amarjot Kaur Grewal Suad Hamdan Almasoudi Ahmad H Almehmadi Bshra A. Alsfouk Amit Kumar Varinder Singh Athanasios Alexiou Marios Papadakis Nermeen N. Welson Thakur Gurjeet Singh Gaber El-Saber Batiha |
| author_sort | Darshpreet Kaur |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is responsible for more than 80% of cases of dementia in senior individuals globally. In the current study, the role of modulation of the FGF1/PI3K/Akt pathway in the protective effect of tozasertib was evaluated. Experimental dementia was induced in mice by injecting streptozotocin (STZ) intracerebroventricularly. Various biochemical parameters for oxidative stress & lipid peroxidation (SOD, GSH, catalase, TBARS), neuroinflammation (MPO, IL-6, IL-1 β, TNF-α, NFκB), apoptotic markers (Bax, Bcl-2, Caspase-3), and memory parameters (AChE activity, β1–40 levels) were assessed. The behavioral parameters evaluated included the Morris Water Maze test and the step-down passive avoidance test. Histological changes were assessed using H&E staining. ICV STZ-induced AD resulted in increased oxidative stress, lipid peroxidation, neuroinflammation, apoptosis, and decreased learning and memory. The results showed that administration of tozasertib improved memory, decreased levels of oxidative stress, inflammatory parameters, and apoptotic markers, and improved histological parameters in a dose-dependent manner. Pre-administration of LY294002, a PI3K/Akt pathway inhibitor, partially reversed the protective effects of Tozasertib, suggesting possible involvement of this pathway. However, as the mechanism was inferred primarily through pharmacological antagonism, further studies including direct molecular assessments (e.g. p-Akt/t-Akt) are warranted to confirm the role of FGF1/PI3K/Akt signaling in Tozasertib’s action. |
| format | Article |
| id | doaj-art-b6d8100826bf4a57bd12aa7dac67aba1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b6d8100826bf4a57bd12aa7dac67aba12025-08-20T04:01:51ZengNature PortfolioScientific Reports2045-23222025-08-0115111610.1038/s41598-025-13920-5Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice modelDarshpreet Kaur0Amarjot Kaur Grewal1Suad Hamdan Almasoudi2Ahmad H Almehmadi3Bshra A. Alsfouk4Amit Kumar5Varinder Singh6Athanasios Alexiou7Marios Papadakis8Nermeen N. Welson9Thakur Gurjeet Singh10Gaber El-Saber Batiha11Chitkara College of Pharmacy, Chitkara UniversityChitkara College of Pharmacy, Chitkara UniversityDepartment of Biology, College of Sciences, Umm Al-Qura UniversityOral Biology Department, Faculty of Dentistry, King Abdulaziz UniversityDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman UniversityChitkara College of Pharmacy, Chitkara UniversityDepartment of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical UniversityUniversity Centre for Research & Development, Chandigarh UniversityUniversity Hospital Witten-HerdeckeDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef UniversityChitkara College of Pharmacy, Chitkara UniversityDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour UniversityAbstract Alzheimer’s disease (AD) is responsible for more than 80% of cases of dementia in senior individuals globally. In the current study, the role of modulation of the FGF1/PI3K/Akt pathway in the protective effect of tozasertib was evaluated. Experimental dementia was induced in mice by injecting streptozotocin (STZ) intracerebroventricularly. Various biochemical parameters for oxidative stress & lipid peroxidation (SOD, GSH, catalase, TBARS), neuroinflammation (MPO, IL-6, IL-1 β, TNF-α, NFκB), apoptotic markers (Bax, Bcl-2, Caspase-3), and memory parameters (AChE activity, β1–40 levels) were assessed. The behavioral parameters evaluated included the Morris Water Maze test and the step-down passive avoidance test. Histological changes were assessed using H&E staining. ICV STZ-induced AD resulted in increased oxidative stress, lipid peroxidation, neuroinflammation, apoptosis, and decreased learning and memory. The results showed that administration of tozasertib improved memory, decreased levels of oxidative stress, inflammatory parameters, and apoptotic markers, and improved histological parameters in a dose-dependent manner. Pre-administration of LY294002, a PI3K/Akt pathway inhibitor, partially reversed the protective effects of Tozasertib, suggesting possible involvement of this pathway. However, as the mechanism was inferred primarily through pharmacological antagonism, further studies including direct molecular assessments (e.g. p-Akt/t-Akt) are warranted to confirm the role of FGF1/PI3K/Akt signaling in Tozasertib’s action.https://doi.org/10.1038/s41598-025-13920-5TozasertibAlzheimer’s diseaseFGF1/PI3K/Akt pathwayStreptozotocinOxidative stressNeuroinflammation |
| spellingShingle | Darshpreet Kaur Amarjot Kaur Grewal Suad Hamdan Almasoudi Ahmad H Almehmadi Bshra A. Alsfouk Amit Kumar Varinder Singh Athanasios Alexiou Marios Papadakis Nermeen N. Welson Thakur Gurjeet Singh Gaber El-Saber Batiha Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model Scientific Reports Tozasertib Alzheimer’s disease FGF1/PI3K/Akt pathway Streptozotocin Oxidative stress Neuroinflammation |
| title | Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model |
| title_full | Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model |
| title_fullStr | Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model |
| title_full_unstemmed | Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model |
| title_short | Neuroprotective effect of Tozasertib in Streptozotocin-induced alzheimer’s mice model |
| title_sort | neuroprotective effect of tozasertib in streptozotocin induced alzheimer s mice model |
| topic | Tozasertib Alzheimer’s disease FGF1/PI3K/Akt pathway Streptozotocin Oxidative stress Neuroinflammation |
| url | https://doi.org/10.1038/s41598-025-13920-5 |
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