Washington, DC (10/10/00)- Three neuroscientists will share
this year's Nobel Prize for medicine for their pioneering studies of neurotransmitters,
research that led the way to a better understanding of neurological diseases
and the developments of treatments for Parkinson's disease and depression.
The new laureates are Arvid Carlsson, Department of Pharmacology, University
of Gothenburg; Paul Greengard, Laboratory of Molecular and Cellular Science,
Rockefeller University, New York; and Eric Kandel, Center for Neurobiology
and Behavior, Columbia University, New York.
Each of the awardees was recognized for his specific contributions to the
understanding of how nerve cells communicate. In particular, the scientists
all helped elucidate one type of signal transduction known as slow synaptic
transmission. The neurotransmitter dopamine plays a key role in this process.
Some of the drugs that were developed thanks to the research in this area
include L-Dopa, a standard treatment for Parkinson's disease, and the antidepressant
fluoxetine (Prozac).
Dr. Carlsson is credited for the critical discovery that dopamine is a transmitter
in the brain that plays an essential role in muscle movement. He has also
mad important discoveries regarding the pathogenesis of schizophrenia. Dr.
Greengard's research elaborated the mechanism of action of dopamine and other
transmitters. He determined that a neurotransmitter interacts with a cell
surface receptor, triggering a cascade of reactions that activate regulatory
proteins. Phosphorylation and dephosphorylation of these proteins changes
their shape and function, facilitating the transmission of signals through
the nervous system. Dr. Kandel, for his part, made important discoveries regarding
the modification of the efficiency of synapses, providing important new information
on short and long-term memory.
Key Elements of the Research
Dopamine
nerve pathways in the brain. Arvid Carlsson showed that there were particularly
high levels of the chemical transmitter dopamine in the so called basal ganglia
of the brain, which are of major importance for instance for the control of
our muscle movements. In Parkinson's disease those dopamine producing nerve
cells whose nerve fibers project to the basal ganglia die. This causes symptoms
such as tremor, muscle rigidity and a decreased ability to move about. Click
Image to Enlarge
A
message from one nerve cell to another is transmitted with the help of different
chemical transmitters. This occurs at specific points of contact, synapses,
between the nerve cells. The chemical transmitter dopamine is formed from
the precursors tyrosine and L-dopa and is stored in vesicles in the nerve
endings. When a nerve impulse causes the vesicles to empty, dopamine receptors
in the membrane of the receiving cell are influenced such that the message
is carried further into the cell. In the treatment of Parkinson's disease,
the drug L-dopa is given, and is converted to dopamine in the brain. This
compensates for the patient's lack of dopamine. Click
Image to Enlarge
Paul
Greengard has shown how dopamine and several other chemical transmitters exert
their effects in the nerve cell. When receptors in the cell membrane are influenced
by a chemical transmitter, the levels of for example the messenger molecule
cAMP are elevated. This activates so called protein kinases, which cause certain
"key proteins" to become phosphorylated, that is phosphate molecules
are added. These protein phosphorylations lead to changes of a number of proteins
with different functions in the cell. When for instance proteins in ion channels
in the cell membrane are influenced, the excitability of a nerve cell and
its ability to send impulses along its branches changes. Click Image to
Enlarge
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