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Mechanism of transmitter release (secretion)

Voltage sensitive calcium channels: structural, molecular properties and interactions with synaptic proteins

Development of anti-Parkinson's, anti-Alzheimer's drugs and drugs for the treatment of stroke





A novel approach for the treatment of Alzheimer's Disease


The devastating, irreversible of most brain, spinal cord and peripheral nerve damage is the prime object for novel developing novel drugs. Currently there are no effective therapies to prevent or reverse neuro-degenerative processes, aging, brain damage, or disease-induced neuropathies. One of the most encouraging approaches for the treatments of Alzheimer and Parkinson's diseases is to destroy the excessive accumulation of free radicals that are responsible for the brain damage.

We are in the process of developing novel pharmaceuticals antioxidants that penetrate the brain blood barrier, for treatment and prevention of neuronal lesions during the onset of neuro-degenerative diseases of the central nervous system for long and better life quality.

The availability of a neuroprotective drug that crosses to the brain will affect the entire field of clinical stroke research; it will provide a preventive approach to treat the onset of Parkinson and Alzheimer's diseases and increase life expectancy with good quality of life. The project aims at producing a neuroprotective drug(s) that will limit the damage of free radicals during neurodegeneration and aging.


Development of anti-Parkinson's and anti-Alzheimer's drugs

A new drug against Parkinson's disease was designed, synthesized and used successfully in animals. This potential drug was further developed by a pharmaceutical company (TEVA Ltd), patented and is now in PHASE III clinical trials in the US and in Europe. Development of new drugs for treatment of stroke is now in progress. A start-up company was recently established to develop these lead compounds to become potential anti stroke drugs.


Mechanism of transmitter release (secretion)

The involvement of calcium channels in secretion is explored by reconstituting channels and synaptic proteins in Xenopus oocytes and PC 12 cells. Electrphysiological and biochemical approachs to study channel kinetics and protein expression. Cloning and cDNA construction for exploring by binding of recombinant fusion proteins specific domains relevant for the release process.

Voltage sensitive calcium channels interact with synaptic proteins (SNAREs) such as syntaxin, SNAP-25 and VAMP in addition to interacting with synaptotagmin. The cRNAs of the channel subunits and the corresponding synaptic proteins are injected into Xenopus oocytes and their interactions are determined electrophysiologically. Modifications of the kinetic properties of voltage sensitive calcium channels determine the regulatory role of the channel in the release process and these recordings allows domain analysis and temporal analysis of the various steps leading to membrane fusion.




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