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Computational Search for A Cure Against Brain-Eating Amoeba

Jacopo Zattoni

Computational Search for A Cure Against Brain-Eating Amoeba.

Rel. Jacek Adam Tuszynski. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2023

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Restricted to: Repository staff only until 23 September 2024 (embargo date).
Licenza: Creative Commons Attribution Non-commercial No Derivatives.

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Abstract:

Naegleria Fowleri is a thermophilic, free-living amoeba of the genus Naegleria. Also known as "brain-eating" amoeba, it is capable of infecting animals' and humans' nervous systems when contaminated water is inhaled. Upon reaching the brain, the amoeba digests the host’s nervous cells, provoking a condition called Primary Amoebic Meningoencephalitis (PAM): diffuse brain hemorrhage, inflammation and swelling, that impair the host’s cognitive abilities and eventually lead to its death within two weeks of the infection’s onset. The current treatment's efficacy is highly dependent on the speed of diagnosis, and is hampered by the low specificity of the drugs used as well as the need to cross the blood-brain barrier (BBB). Together with the infection’s nonspecific symptoms, these aspects are responsible for the worryingly high mortality rate, above 95%. Nonetheless, N. Fowleri’s infection is quite rare. About 300 cases have been documented worldwide since 1965, although it’s presumably under-diagnosed. Its presence has been documented anywhere but Antarctica, and the rising temperature caused by global warming is expected to increase its incidence. The mechanisms responsible for its pathogenicity are still unclear. The scientific community agrees that the most promising therapy is the targeting of the amoeba's microtubules, in a similar fashion to cancer chemotherapy. Anyway, its clinical applicability is currently on hold, due to the reported in vitro inefficacy of a group of well-known microtubule-targeting agents (MTAs). The present study aims at providing insight into N. Fowleri's tubulins mutations, with particular attention to known MTAs' binding sites. Homology modelling was employed to model the amoeba's tubulins, and a library of putative, colchicine site-targeting ligands was designed. Finally, docking simulations were used to assess their affinity for N. Fowleri's tubulins, as well as the most promising ligands' selectivity between human and the amoeba's tubulins.

Relators: Jacek Adam Tuszynski
Academic year: 2022/23
Publication type: Electronic
Number of Pages: 168
Subjects:
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: UNSPECIFIED
URI: http://webthesis.biblio.polito.it/id/eprint/26226
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