Genetics of Neurodegenerative Diseases (2602)

Assoc. prof.dr.sc. Silva Katušić Hećimović, zn. Counsellor

Ruđer Boskovic Institute

To understand the molecular-genetic basis of neurodegenerative diseases, i.e. different mechanisms of diseases, and the role of animal models for the development of new methods of treatment.

This course would deal with the following thematic units: The concept of neurodegenerative diseases, their similarities and differences: this thematic whole will, on the examples of several neurodegenerative diseases, such as Huntington's disease, Alzheimer's disease, Parkinson's disease and "prion" disease, clarify their similarities and differences related to the pathology of the disease, morphological changes in the brain and the mechanism of the onset of the disease; Genetics of neurodegenerative diseases: this thematic unit will process new insights into the genetics of neurodegenerative diseases, in doing so, examples of the above diseases will be used and the genetic basis of hereditary and sporadic forms of neurodegenerative diseases will be clarified as well as the difference between monogenic and complex neurodegenerative diseases including the methods used for their genetic detection as well as the detection of unknown genes; Molecular and cellular biology of neurodegenerative diseases: this thematic unit will give insight into the possible mechanisms of the neurodegeneration process and, on the examples of Huntington, Alzheimer's and prion diseases, will clarify the assumed hypotheses of the molecular basis of the onset of the disease, will explain pathological changes at the level of the neuronal cell and give insight into the functions of key proteins; Animal models of neurodegenerative diseases: this thematic unit will give knowledge about existing animal models of neurodegenerative diseases and how well or badly individual animal models replicate a particular disease as well as their application in the research of new treatment options for the disease; New possibilities for therapy for neurodegenerative diseases: on the examples of Azheimer disease, Parkinson's disease and Huntington's disease, new treatment options for these diseases will be described and knowledge will be given about the latest results of their application in clinical trials.

1. Explain the gene bases of neurodegenerative hereditary and complex forms of the disease.
2. Analyze the molecular aspects of neurodegeneration.
3. Rethink the role and meaning of animal models for the development of new treatment methods.
4. Extract relevant data and information from the Internet for the purpose of researching the gene and molecular background of neurodegenerative diseases and biomarkers with a view to their early detection and monitoring of progression and/or therapeutic effect.

Regular attendance with possible justified absence of up to 2 hours of classes.

Book:
1. Chesselet M-F: Molecular Mechanisms of Neurodegenerative Disorders (2000) Humana Press.
2. Bear MF, Connors BW, Paradiso, MA: Neuroscience – Exploring the Brain, 2nd edition (2001) lippincott Williams & Wilkins, Philadelphia (PA).
3. Harper PS, Perutz M: Glutamine repeats and neurodegenerative diseases. molecular aspects, 1st edition (2001) Oxford University Press Inc., New York, NY.

Original scientific papers:
1. Zufiría M, Gil-Bea FJ, Fernández-Torrón R, Poza JJ, Muñoz-Blanco JL, Rojas-García R, Riancho J, de Munain AL. ALS: A bucket of genes, environment, metabolism and unknown ingredients. Prog Neurobiol. 2016 May 25th pii: S0301-0082(15)30090-3. doi: 10.1016/j.pneurobio.2016.05.004.
2. Thompson AG, Gray E, Heman-Ackah SM, Mäger I, Talbot K, Andaloussi SE, Wood MJ, Turner MR. Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers. Nat Rev Neurol. 2016 Jun;12(6):346-57. doi: 10.1038/nrneurol.2016.68.
3. Hernandez DG, Reed X, Singleton AB. Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. J Neurochem. 2016 Apr 18th doi: 10.1111/jnc.13593
4. Hardy J. Catastrophic cliffs: a partial suggestion for selective vulnerability in neurodegenerative diseases. Biochem Soc Trans. 2016 Apr 15,44(2):659-61.
5. Leung C, Jia Z. Mouse Genetic Models of Human Brain Disorders. Front Genet. 2016 Mar 23;7:40. doi: 10.3389/fgene.2016.00040.
6. Cacace R, Sleegers K, Van Broeckhoven C. Molecular genetics of early-onset Alzheimer's disease revisited. Alzheimer's Dement. 2016 Mar 24. pii: S1552-5260(16)00079-0. doi: 10.1016/j.jalz.2016.01.012.
7. Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM. Alzheimer's disease. Lancet. 2016 Feb 23. pii: S0140-6736(15)01124-1. doi: 10.1016/S0140-6736(15)01124-1.
8. Iqbal K, Liu F, Gong CX. Tau and neurodegenerative disease: the story so far. Nat Rev Neurol. 2016 Jan;12(1):15-27. doi: 10.1038/nrneurol.2015.225. Epub 2015 Dec 4.
9. Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet. 2015 Oct 24,386(10004):1672-82. doi: 10.1016/S0140-6736(15)00461-4.

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Monitoring of the quality and performance of the course will be evaluated for individual lectures, i.e. for the course. thematic units and for the entire subject, and at the same time the success of the course will be evaluated annually by the joint expert committee of the Rudjer Boskovic Institute, the University of Dubrovnik and the University of Osijek.