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ADE - CEREBROVASCULAR MALFORMATIONS: PATHOGENETIC MECHANISM AND THERAPEUTIC STRATEGIES

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CEREBROVASCULAR MALFORMATIONS: PATHOGENETIC MECHANISM AND THERAPEUTIC STRATEGIES

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Academic year 2023/2024

Course ID
SCB0364
Teacher
Saverio Francesco Retta (Lecturer)
Year
3rd year
Teaching period
Second semester
Type
Elective
Credits/Recognition
1
Course disciplinary sector (SSD)
BIO/13 - experimental biology
MED/03 - medical genetics
MED/04 - experimental medicine and pathophysiology
MED/26 - neurology
MED/27 - neurosurgery
MED/37 - neuroradiology
Delivery
Lecture
Language
English
Attendance
Mandatory
Type of examination
Oral
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Sommario del corso

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News

Cerebrovascular malformations: Natural history, pathogenetic mechanisms and therapeutic strategies
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Course objectives

Multidisciplinary elective didactic activity presenting biomedical advancements on cerebrovascular diseases, with a major focus on cerebrovascular malformations.

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Results of learning outcomes

Knowledge of biomedical advancements on cerebrovascular diseases, with a major focus on cerebrovascular malformations.

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Program

Multidisciplinary Elective Didactic Activity (EDA/ADE)
Cerebrovascular malformations: pathogenic mechanisms and therapeutic strategies

  • Marco Fontanella (Neurosurgery) (Department of Medical-Surgical Specialties, University of Brescia, Italy)
    Clinical and neurosurgical features of Cerebral Cavernous Malformation (CCM) disease

 

  • Saverio Francesco Retta (Applied Biology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
    From genes to targeted therapies: the long climb to the cure of Cerebral Cavernous Malformation (CCM) disease

 

  • Angela Glading (Cell Biology) (Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA)
    The Multifaceted Roles of the Scaffold Protein KRIT1/CCM1: A Master Regulator of Cerebrovascular Quiescence

 

  • Giovanni Battista Ferrero (Clinical Genetics) (Department of Clinical and Biological Sciences, University of Torino)
    The potential of Next-Generation Sequencing (NGS) technology: comprehensive whole-genome and whole-exome profiling to identify genetic variants

 

  • Souvik Kar (Molecular Biology) (International Neuroscience Institute, Hannover, Germany)
    Non-coding RNA repertoires in Cerebral Cavernous Malformations: identification and role in disease pathogenesis

 

  • Carmelo Sturiale (Neurosurgery) (Catholic University of the Sacred Heart, Rome, Italy)
    Neurosurgical treatment of the main Cerebrovascular Malformations

 

  • Paola Gamba (General Pathology) (Department of Clinical and Biological Sciences, University of Torino, Italy)
    Brain Cholesterol Dysmetabolism: a Key Feature in Neurodegeneration and Brain Diseases

 

  • Eva Faurobert (Cellular Mechanotransduction) (Institute for Advanced Biosciences, University Grenoble Alpes, Grenoble, France)
    Role of mechanotransduction in the pathogenesis of Cerebral Cavernous Malformations: molecular and cellular aspects

 

  • Carla Olivieri (Applied Biology) (Department of Molecular Medicine, University of Pavia, Italy)
    Cerebral Arteriovenous Malformation in a rare disease: the story of Hereditary Hemorrhagic Telangiectasia (HHT)

 

  • Cinzia Antognelli (Applied Biology) (Department of Medicine and Surgery, University of Perugia, Italy)
    Glycative Stress in Health and Disease

 

  • Andrea Perrelli (Applied Biology) (Department of Clinical and Biological Sciences, University of TorinoDepartment of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA)
    Towards precision nanomedicine for CCM disease
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Course delivery

  • Face-to-face lectures/seminars
  • Streaming (Webex/Zoom) lectures/seminars held by national and international experts in the field of cerebrovascular diseases 
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Learning assessment methods

As an Elective Didactic Activity (ADE) chosen by the student, this ADE aims to personalize the student's educational path on the basis of their inclinations and interests, deepening specific knowledge and training aspects by discussion of topics that are not included in the "core curriculum" of the Integrated Courses.

The acquisition of the credits assigned to ADE takes place only upon reaching 100% of attendance.

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Support activities

Seminars of experts in the field of cerebrovascular diseases

Suggested readings and bibliography

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  1. Fontanella MM, Bacigaluppi S, Doglietto F, Zanin L, Agosti E, Panciani P, Belotti F, Saraceno G, Spena G, Draghi R, Fiorindi A, Cornali C, Biroli A, Kivelev J, Chiesa M, Retta SF, Gasparotti R, Kato Y, Hernesniemi J, Rigamonti D. (2021) An international call for a new grading system for cerebral and cerebellar cavernomasJ Neurosurg Sci. 2021 Jun;65(3):239-246.
  2. Perrelli A, Retta SF*. (2021). Polymorphisms in genes related to oxidative stress and inflammation: Emerging links with the pathogenesis and severity of Cerebral Cavernous Malformation diseaseFree Radic Biol Med. 2021 Aug 20;172:403-417.
  3. De Luca E, Perrelli A, Swamy H, Nitti M, Passalacqua M, Furfaro AL, Salzano AM, Scaloni A, Glading AJ, Retta SF*. (2021). Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1J Cell Sci. 2021 Feb 4;134(3):jcs250217.
  4. Perrelli A, Fatehbasharzad P, Benedetti V, Ferraris C, Fontanella M, De Luca E, Moglianetti M, Battaglia L, Retta SF*. (2021). Towards precision nanomedicine for cerebrovascular diseases with emphasis on Cerebral Cavernous Malformation (CCM). Expert Opinion on Drug Delivery. 2021 Jan 23:1-28.
  5. Kim AH, Perrelli A, Ragni A, Retta F, De Silva TM, Sobey GC, Retta SF*. (2020). Vitamin D Deficiency and the Risk of Cerebrovascular Disease. Antioxidants (Basel). 2020 Apr 17; 9(4), pii: E327; doi:10.3390/antiox9040327.
  6. Retta SF*, Perrelli A, Trabalzini L, Finetti F. (2020). From Genes and Mechanisms to Molecular-Targeted Therapies: The Long Climb to the Cure of Cerebral Cavernous Malformation (CCM) Disease. Methods Mol Biol. 2020;2152:3-25. doi: 10.1007/978-1-0716-0640-7_1.
  7. Antognelli C, Perrelli A, Armeni T, Nicola Talesa V, Retta SF*. (2020). Dicarbonyl Stress and S-Glutathionylation in Cerebrovascular Diseases: A Focus on Cerebral Cavernous Malformations. Antioxidants (Basel). 2020 Feb 1; 9(2). pii: E124. doi: 10.3390/antiox9020124.
  8. Vieceli Dalla Sega F, Mastrocola R, Aquila G, Fortini F, Fornelli C, Zotta A, Cento AS, Perrelli A, Boda E, Pannuti A, Marchi S, Pinton P, Ferrari R, Rizzo P, Retta SF*. (2019). KRIT1 Deficiency Promotes Aortic Endothelial Dysfunction. Int J Mol Sci. 2019 Oct 5; pii: E4930. doi:c10.3390/ijms20194930.
  9. Cianfruglia L, Perrelli A, Fornelli C, Magini A, Gorbi S, Salzano AM, Antognelli C, Retta F, Benedetti V, Cassoni P, Emiliani C, Principato G, Scaloni A, Armeni T, Retta SF*. (2019). KRIT1 Loss-Of-Function Associated with Cerebral Cavernous Malformation Disease Leads to Enhanced S-Glutathionylation of Distinct Structural and Regulatory Proteins. Antioxidants (Basel). 2019 Jan 17;8(1):1-28.
  10. De Luca E, Pedone D, Moglianetti M, Pulcini D, Perrelli A, Retta SF* & Pompa PP (2018). Multifunctional Platinum@BSA-Rapamycin Nanocarriers for the Combinatorial Therapy of Cerebral Cavernous Malformation. ACS Omega, 2018 Nov 30;3(11):15389-15398.
  11. Perrelli A, Goitre L, Salzano AM, Moglia A, Scaloni A, and Retta SF*. (2018). Biological Activities, Health Benefits, and Therapeutic Properties of Avenanthramides: From Skin Protection to Prevention and Treatment of Cerebrovascular Diseases. Oxidative Medicine and Cellular Longevity 2018, 6015351.
  12. Antognelli C, Trapani E, Delle Monache S, Perrelli A, Daga M, Pizzimenti S, Barrera G, Cassoni P, Angelucci A, Trabalzini L, Talesa VN, Goitre L, Retta SF*. (2018). KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: Implication for Cerebral Cavernous Malformation disease. Free Radical Biology and Medicine 2018 Feb 1; 115:202-218. Epub 2017 Nov 21.
  13. Antognelli C, Trapani E, Delle Monache S, Perrelli A, Fornelli C, Retta F, Cassoni P, Talesa VN, Retta SF*. (2017). Data in support of sustained upregulation of adaptive redox homeostasis mechanisms caused by KRIT1 loss-of-function. Data Brief. 2017 Dec 13; 16:929-938.
  14. Goitre L, DiStefano PV, Moglia A, Nobiletti N, Baldini E, Trabalzini L, Keubel J, Trapani E, Shuvaev VV, Muzykantov VR, Sarelius IH, Retta SF* & Glading AJ. (2017). Up-regulation of NADPH oxidase-mediated redox signaling contributes to the loss of barrier function in KRIT1 deficient endothelium. Scientific Reports, 2017 Aug 15; 7(1):8296.
  15. Retta SF* and Glading AJ. (2016). Oxidative stress and inflammation in cerebral cavernous malformation disease pathogenesis: Two sides of the same coin. International Journal of Biochemistry & Cell Biolology. 2016 Dec; 81(Pt B):254-270.
  16. Marchi S, Trapani E, Corricelli M, Goitre L, Pinton P, Retta SF*. (2016). Beyond Multiple Mechanisms and a Unique Drug: Defective Autophagy as Pivotal Player in Cerebral Cavernous Malformation Pathogenesis and Implications for Targeted Therapies. Rare Diseases, 2016 Jan 25; 4:1, e1142640.
  17. Marchi S, Retta SF*, Pinton P. (2016). Cellular processes underlying cerebral cavernous malformations: Autophagy as another point of view. Autophagy, 2016 Feb; 12(2):424-5.
  18. Moglianetti M, De Luca E, Pedone D, Marotta R, Catelani T, Sartori B, Amenitsch H, Retta SF, Pompa PP. (2016). Platinum nanozymes recover cellular ROS homeostasis in oxidative stress-mediated disease model. Nanoscale, 2016 Feb 14; 8(6):3739-52.
  19. Choquet H, Trapani E, Goitre L, Trabalzini L, Akers A., Fontanella M, Hart BL, Morrison LA, Pawlikowska L, Kim H, Retta SF*. (2016). Cytochrome P450 and matrix metalloproteinase genetic modifiers of disease severity in Cerebral Cavernous Malformation type 1. Free Radical Biology and Medicine, 2016 Jan 19; 92:100-109.
  20. Marchi S, Corricelli M, Trapani E, Bravi L, Pittaro A, Delle Monache S, Ferroni L, Patergnani S, Missiroli S, Goitre L, Trabalzini L, Rimessi A, Giorgi C, Zavan B, Cassoni P, Dejana E, Retta SF*, Pinton P. (2015). Defective autophagy is a key feature of cerebral cavernous malformations. EMBO Molecular Medicine, 2015. 7(11):1403-1417.
  21. Trapani E, Retta SF*. (2015). Cerebral cavernous malformation (CCM) disease: from monogenic forms to genetic susceptibility factors. Journal of Neurosurgical Sciences, 2015 Sep; 59(3):201-9.
  22. Gibson C., Zhu W., Davis C.T., Bowman-Kirigin J.A., Chan A.C., Ling J., Walker A.E., Goitre L., Delle Monache S., Retta S.F., Shiu Y-T E., Grossmann A.H., Thomas K.R., Donato A.J., Lesniewski L.A., Whitehead K.J., Li D.J. (2015) Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation. Circulation, 2015; 131(3):289-99.
  23. Fontanella MM, Panciani PP, Spena G, Roca E, Migliorati K, Ambrosi C, Sturiale CL, Retta SF (2015) Professional athletes and cerebral cavernomas: an obstacle to overcome. Journal of Sports Medicine and Physical Fitness, 2015 Sep; 55(9):1046-7.
  24. Goitre L, De Luca E, Braggion S, Trapani E, Guglielmotto M, Biasi F, Forni M, Moglia A, Trabalzini L, Retta SF*. (2014) KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun. Free Radical Biology and Medicine, 2014 Mar; 68:134-47.
  25. Maddaluno L, Rudini N, Cuttano R, Bravi L, Giampietro C, Corada M, Ferrarini L, Orsenigo F, Papa E, Boulday G, Tournier-Lasserve E, Chapon F, Richichi C, Retta SF, Lampugnani MG, Dejana E. (2013) EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature,2013; 498(7455):492-6.
  26. Bacigaluppi S, Retta S.F., Pileggi S, Fontanella M, Goitre L, Tassi L, La Camera A, Citterio A, Patrosso MC, Tredici G, Penco S. (2013) Genetic and cellular basis of Cerebral Cavernous Malformations: implications for clinical management. Clinical Genetics, 2013; 83(1):7-14.
  27. D’Angelo R., Marini V., Rinaldi C., Origone P., Dorcaratto A., Avolio M., Goitre L., Forni M., Capra V., Alataci C., Mareni C., Garrè C., Bramanti P., Sidoti A., Retta S.F.*, Amato A. (2011). Mutation Analysis of CCM1, CCM2 and CCM3 Genes in a Cohort of Italian Patients with Cerebral Cavernous Malformation. Brain Pathology, 2011; 21(2): 215-;224.
  28. Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P., Retta S.F.* (2010). KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species. PLoS One, 2010; 5(7):e11786.


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Notes

  • Maximum number of students: 40
  • Schedule: from April 9th to April 22th, 2024
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Class scheduleV

Lessons: from 09/04/2024 to 22/04/2024

Notes: April 9th: from h. 09:00 to 12:00 and from 14:00 to 16:00
April 10th: from h. 09:00 to 13:00 and from 15:00 to 16:00
April 12th: from h. 09:00 to 10:00
April 22nd: from h. 10:00 to 11:00

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Last update: 05/04/2024 10:25
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