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Parkinson’s-disease, in the dogfish shark the molecule for a new therapeutic strategy

Published in PNAS a study involving a research team from Unifi

Squalamine, a synthesized steroid mirroring one naturally made by the dogfish shark, could be a new potential compound for therapeutic intervention in Parkinson’s disease (PD). This finding was recently published online in the Proceedings of the National Academy of Sciences (PNAS) with the title "A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity" (DOI: doi: 10.1073 / pnas.1610586114) by an international research team including authors from the Department of Biomedical, Experimental and Clinical Sciences.

 Squalamine prevents the build up of a lethal protein, α-synuclein, which is involved in PD and dementia with Lewy bodies. “In this study – say the co-senior authors Cristina Cecchi and Fabrizio Chiti, Professors of Biochemistry at the University of Florence, together with the researcher Roberta Cascella - a series of in vitro experiments demonstrated that squalamine protects human neuronal cells from the toxicity induced by pre-formed toxic oligomers of α-synuclein, by preventing their binding to the cellular membrane”.

 Squalamine is a well known molecule, which has already been approved by the Food and Drug Administration (FDA) for the treatment of macular degeneration, an age-related disease affecting the macula, a small central portion of the retina.

"In the contest of PD, the properties of this molecule have been discovered in the United States - says Fabrizio Chiti – following the serendipitous observation of rapid clinical improvement in PD patients being treated with squalamine for cancer. This unexpected finding has promoted new clinical trials on PD patients, on the basis of the evidence also obtained at molecular and cellular levels by the research project that involves the Unifi team".

The study put forward new research programs. "New in vitro and in vivo experiments are being performed - concludes Roberta Cascella - on another class of aminosterol analogs of squalamine, which appear more promising for the treatment of PD and other neurodegenerative diseases".

The research project is coordinated by the Department of Chemistry of the University of Cambridge (UK) and involves other co-authors from Cambridge (UK), Washington (United States), Bethesda (United States), Zaragoza (Spain) and Groningen (The Netherlands).

27 February 2017