Download Development of Bi-functional molecules for use in the control and

Development of Bi-functional molecules for use in the control
and treatment of degenerative diseases
Date: 9/04/14
Speaker: Mr. Tzachi Shalit
Department of Biological Chemistry, Ariel University
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder. Parkinson's is
characterized by the following symptoms including resting tremor, rigidity, difficulty
in initiating movement, and postural instability. The molecular mechanisms that
initiate the degeneration of the dopaminergic neurons in the brain stem, particularly in
the SN (substantia nigra- Part of the brain that plays an important role in reward,
addiction, and movement) of PD patients are still unknown. However, oxidative stress
is considered to be primary cause of neuronal degeneration. It has been observed that
Iron can induce oxidative stress inducing progressive Parkinsonism. Monoamine
oxidase enzymes (like MAO-B) metabolize dopamine and playing an important role
in oxidative stress processes. We reasoned that neurodegenerative diseases could be
better addressed using a combination of an iron chelating ligand and a MAO-B
inhibitor in a single bifunctional molecule. We, therefore, developed a new
antioxidant-iron chelator with potent selective MAO-B inhibitory activity to be used
as drug candidates for the treatment and/or prevention of the neurodegenerative
diseases. The design, preparation and preliminary biological results of our novel
inhibitors will be presented and discussed.