ליאת בן מויאל סגל 2006-2007

מוסד לימודים לדוקטורט:
האוניברסיטה העברית בירושלים
תחום אקדמי:
ביוכימיה, פיזיולוגיה
מנחה/מנחים בדוקטורט:
פרופ' חרמונה שורק, פרופ חגי ברגמן
נושא הדוקטורט:
The Role of the Cholinergic System in the Pathogenesis of Parkinson’s Disease
מוסד נוכחי:
בית חולים בילינסון

Liat Benmoyal-Segal is a biochemist and physiologist working at Beilinson Hospital.

Liat is focusing on the involvement of the cholinergic system in the progression of Parkinson’s Disease (PD), particularly from the genetic perspective. Although PD was first described in 1815 by Dr. James Parkinson, its etiology is not fully understood, and no cure has been found.

In her PhD research, Liat initiated experiments to test the working hypothesis that aberrant control of AChE gene expression can influence susceptibility to PD. These tests are performed on transgenic mice that constitutively over-express different AChE variants. Because of their inherited imbalance, applying state-of-the-art techniques in molecular biology to such transgenic models can enable evaluation of the role of specific AChE isoforms and explain the intriguing mechanisms underlying the imbalance between cholinergic and dopaminergic signaling that initiates PD progression. This study will offer a new perspective on the involvement of the failing cholinergic system in the development of PD. EN101 (a specific antisense to AChE) or novel mRNA splicing modulators may become candidate drugs for attenuating the levels of circulating AChE, which may play a role in neurodegenerative diseases such as PD.

In her MSc project, Liat discovered a novel association between genetic polymorphisms in Acetylcholinesterase (AChE, a key enzyme in the cholinergic system) and the occurrence of PD under chronic exposure to organophosphate insecticides (OPs). OPs, commonly used as agricultural pesticides, have been shown to increase the risk of developing PD. Their main target is the inhibition of AChE. Assessment of the environmental risk of neurodegeneration associated with exposure to pesticides is of great significance. Liat's study added important information on such risks and how they can be avoided.

Liat's goal is to find a treatment that would either prevent PD or attenuate its progression. Her findings may also have implications for other neurodegenerative diseases, such as Alzheimer's and Huntington's.