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Inhibiting aggregation of amyloidogenic proteins as a strategy for treating neurodegeneration

Event Details:

  • Date: - -
  • Venue: Collegio A Volta, Pavia
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Daniel Segal of the School of Molecular Cell Biology & Biotechnology, Tel-Aviv University will give a seminar on Wednesday the 25th of July in the lecture theatre of Collegio A Volta (17, via A Ferrata)_ at 12.00 noon.  The  seminar, entitled Inhibiting aggregation of amyloidogenic proteins as a strategy for treating neurodegeneration, will discuss recent work by the speaker in developing approaches targeting the formation of protein aggregates that cause damage to neurons and other cell types.  The poster of the lecture can downloaded here and all students of Biology, Biotechnology and Medicine of Collegio A Volta and members of the Department of Molecular Medicine are strongly encouraged to attend.

Abstract
My laboratory is interested in intrinsically disordered proteins, in particular disease-associated amyloidogenic proteins, and in developing means for inhibiting their harmful aggregation. Insights obtained about structural determinants that facilitate self-assembly of these proteins, such as the role of aromatic residues, serve us for developing small molecules and peptidomimetics to inhibit aggregation of these amyloidogenic proteins and disassemble of pre-existing aggregates. We evaluate efficacy of the candidate inhibitors using a series of in vitro methods, cell-based assays, and studies in transgenic animal models – Drosophila and mice. I will illustrate this approach using three examples: Tryptophan-modified naphthoquinone small molecules towards amyloid-beta and tau involved in Alzheimer’s disease; β-synuclein derived peptidomimetics towards α-synuclein involved in Parkinson’s; and a naturally occurring molecule, Mannitol, against α-synuclein with unexpected lead towards clinical trial. If time permits I will describe recent results of High Throughput screening for novel inhibitors, and the use of computational tools for understanding their mechanism of action.

Biography
Daniel Segal obtained his PhD in Genetics from the Hebrew University, Jerusalem, under the supervision of Prof. Raphael Falk, studying Drosophila developmental genetics. He did his postdoctoral studies at Harvard University, with the late Prof. William Gelbart, working on molecular genetics of the decapentaplegic developmental gene complex in Drosophila. He moved back to Israel as a scientist at the Weizmann Institute working on oncogene homologs in the fruit fly and on neurogenetics. Since 1987 he is a faculty member at Tel-Aviv University, where he is the Head of the School of Molecular Cell Biology & Biotechnology. His lab focuses on intrinsically disordered proteins, in particular disease-associated amyloidogenic proteins, and on developing means for inhibiting their harmful aggregation.

Image
Prior protein fibrils, courtesy of R Moore, Rocky Mountain Laboratories

 

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