From genetic analysis of rare neurological diseases to the study of a translational model of Parkinson’s disease

During my PhD I had the possibility to work in two different laboratories and be involved in two different topics. I spent the first period of the PhD at the department of Medical, Surgical and Neurological Sciences in Siena. Here, I investigated genetics variants found in patients with clinical suspicion of leukoencephalopathies and leukodystrophies. In particular, in the context of molecular diagnosis of CADASIL, CARASIL and Alexander’s disease, patients DNA was screened for mutations in the genes of interest- NOTCH3, HTRA1 and GFAP respectively. The second period of my PhD took place at the department of Clinical Neurosciences in Cambridge, where I worked on characterization of a new mouse model of Parkinson’s disease. Such animal model aimed to reproduce the aggregation of the truncated human α-synuclein (1-120) in the intestine and its spreading to the brain according to Braak’s staging. The work conducted in Siena was carried out in a diagnostics environment, and it allowed the identification, in GFAP gene, of a mutation which is really likely to be pathogenic. In HTRA1 gene, two mutations were detected in compound heterozygosis in a Caucasian patient affected from CARASIL. The results of this work have been published in peer reviewed medical journals and are reported in extenso in the thesis. On the other hand, in Cambridge I had the chance to approach basic research; I gained new practical skills, becoming confident with immunohistochemistry and biochemistry methods, other than acquiring knowledge on Parkinson’s disease. Working in two different fields allowed me to widen my spectrum of knowledge, hence acquiring a more aware working method, , and to carry on basic and clinical applied researches, which was my goals as a PhD student