Pharmacological study of the potential repositioning of some protein kinase inhibitors in experimentally-induced parkinson’s disease in rats / (Record no. 171226)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 06670namaa22004331i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20250413105603.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 250320s2024ua |||a|||frm||| 000 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Original cataloguing agency | EG-GICUC |
| Language of cataloging | eng |
| Transcribing agency | EG-GICUC |
| Modifying agency | EG-GICUC |
| Description conventions | rda |
| 041 0# - LANGUAGE CODE | |
| Language code of text/sound track or separate title | eng |
| Language code of summary or abstract | eng |
| -- | ara |
| 049 ## - Acquisition Source | |
| Acquisition Source | Deposit |
| 082 04 - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 615.77 |
| 092 ## - LOCALLY ASSIGNED DEWEY CALL NUMBER (OCLC) | |
| Classification number | 615.77 |
| Edition number | 21 |
| 097 ## - Degree | |
| Degree | Ph.D |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.09.Ph.D.2024.He.P. |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Heba Mohamed Mohamed Mansour, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Pharmacological study of the potential repositioning of some protein kinase inhibitors in experimentally-induced parkinson’s disease in rats / |
| Statement of responsibility, etc. | By Heba Mohamed Mohamed Mansour; supervision Dr. Mahmoud Khattab, Dr. Aiman El-Khatib, Dr. Ahmed Fathi Mohamed. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | دراسة لإعادة التموضع المحتمل لبعض مثبطات البروتين كيناز في مرض الشلل الرعاش المحدث تجريبيا في الجرذان / |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2024. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 43 pages : |
| Other physical details | illustrations ; |
| Dimensions | 25 cm. + |
| Accompanying material | CD. |
| 336 ## - CONTENT TYPE | |
| Content type term | text |
| Source | rda content |
| 337 ## - MEDIA TYPE | |
| Media type term | Unmediated |
| Source | rdamedia |
| 338 ## - CARRIER TYPE | |
| Carrier type term | volume |
| Source | rdacarrier |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | Thesis (Ph.D)-Cairo University, 2024. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 25-39. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. 10 million people worldwide have PD. Motor impairment seen in PD is associated with dopaminergic neurotoxicity in the striatum. Cell death has a significant effect on the development and progression of PD. Extensive research has unveiled new regulated cell death (RCD) mechanisms that are not dependent on apoptosis such as necroptosis, and ferroptosis. Recently, different kinases have been implicated in the induction of different RCD mechanisms. However, most protein kinase inhibitors (PKIs) have been thoroughly tested for non-CNS disorders such as cancer. PKIs research in PD appears to be lagging more than in other diseases. Therefore, the present research aims to contribute to this growing area of research by investigating the molecular signaling pathways of different RCD mechanisms, including ferroptosis and necroptosis, and examining the efficacy of treatment with lapatinib ditosylate and pazopanib, as PKIs, on motor decline induced by rotenone in male rats. Rats were s.c. injected with 2 mg/kg rotenone prepared as 50X in DMSO and diluted with olive oil. After one hour of rotenone administration, rats were orally administered 100 mg/kg lapatinib dissolved in 10% Tween in saline, or 15 mg/kg pazopanib dissolved in 0.5% Tween in saline. Administration of lapatinib and pazopanib for 21 days rescued motor dysfunctions as proved by enhancement of behavioral performance in rota-rod, grip-strength, and open-field tests. They also debilitated histopathological alterations induced by rotenone intoxication, along with increased dopamine levels and dopaminergic neuronal survival as indicated by increased tyrosine hydroxylase. Lapatinib and pazopanib exerted neuroprotective effects through inhibition of ferroptosis as indicated by inhibited ferroptotic PKC-βII/PLC-γ-ACSL4 pathway, suppressed iron, 4-Hydroxynonenal (4-HNE), and prostaglandin-endoperoxide synthase 2 (PTGS2), along with increased glutathione (GSH), and glutathione peroxidase-4 (Gpx4). Pazopanib has anti-necroptotic effects through inhibition of p-RIPK1/p-RIPK3/p-MLKL pathway. Also, lapatinib and pazopanib modulate heat shock protein 90/cell cycle division 37 (HSP90/CDC37), and their clients, including c-abl, src, and leucine-rich repeat kinase 2 (LRRK2). As an epilogue, the present study provides an important opportunity to advance the understanding of the repurposing of PKIs as a disease-modifying agent for PD. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | يعد مرض الشلل الرعاش ثاني أكثر الأمراض العصبية شيوعا في العالم بعد مرض الزهايمر. ويسبب الشلل الرعاش اضطراب يتفاقم تدريجيًا يؤثر على الجهاز العصبي وأجزاء الجسم التي تسيطر عليها الأعصاب. وقد يكون أول الأعراض ظهورًا رُعاش لا يكاد يُلحظ في يد واحدة فقط ثم تتطور الأعراض لتشمل تيبس في العضلات وبطء في الحركة واختلال في وضعية الجسم والاتزان وتغيرات الكلام مثل التلعثم ، ويكون المريض عرضة للإصابة بأعراض غير عصبية مثل الإمساك واضطرابات النوم والاكتئاب. حتي الان لا يوجد علاج لمرض الشلل الرعاش ولكن توجد بعض الأدوية التي تخفف من حدة الأعراض والتي تعتمد علي زيادة نسبة الدوبامين في المخ. يتميز مرض الشلل الرعاش بموت أعصاب الدوبامين داخل النسيج المخطط بالدماغ مع نقص ملحوظ في كمية الدوبامين. كما يتميز أيضا بتراكم بروتينات تسمي الفا سينيوكلين وهو المكون الرئيسي لأجسم ليوي. تم اكتشاف حدوث موت الخلايا المنتظم كأحد مسببات مرض الشلل الرعاش، لذا فإن معرفة أسباب وماهية حدوث موت الخلايا المنتظم واستخدام مثبطات له يعد من الطرق الجديدة لعلاج مرض الشلل الرعاش. كان استخدام مثبطات البروتين كيناز مقتصرا علي مجال الأورام في الثلاثين عاما الماضية، وبالرغم أن عدد من الأبحاث اثبت وجود علاقة وطيدة بين زيادة بعض من البروتين كيناز وموت الخلايا المنتظم، إلا انه لا يوجد أبحاث كافية عن تأثير استخدام مثبطات البروتين كيناز علي موت الخلايا المنتظم في مرض الشلل الرعاش. |
| 530 ## - ADDITIONAL PHYSICAL FORM AVAILABLE NOTE | |
| Issues CD | Issued also as CD |
| 546 ## - LANGUAGE NOTE | |
| Text Language | Text in English and abstract in English. |
| 650 #7 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | Drugs affecting the musculoskeletal system |
| Source of heading or term | qrmak |
| 653 #0 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Parkinson’s disease |
| -- | ferroptosis |
| -- | necroptosis |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Mahmoud Khattab |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Aiman El-Khatib |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ahmed Fathi Mohamed |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2024 |
| Supervisory body | Mahmoud Khattab |
| -- | Aiman El-Khatib |
| -- | Ahmed Fathi Mohamed |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmacology and Toxicology |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Sara Salah |
| Reviser Names | Eman Ghareb |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Dewey Decimal Classification |
| Koha item type | Thesis |
| Edition | 21 |
| Suppress in OPAC | No |
| Source of classification or shelving scheme | Home library | Current library | Date acquired | Inventory number | Full call number | Barcode | Date last seen | Effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|
| Dewey Decimal Classification | المكتبة المركزبة الجديدة - جامعة القاهرة | قاعة الرسائل الجامعية - الدور الاول | 20.03.2025 | 90967 | Cai01.08.09.Ph.D.2024.He.P. | 01010110090967000 | 20.03.2025 | 20.03.2025 | Thesis |