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EINBLICKE
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When Alois Alzheimer presented the case of a patient who
had died in a mentally deranged state at the "37thMeeting of
South-West German Psychiatrists" in Tübingen on November
3, 1906,
he could never have imagined that the dementia
illness that was later named after him would become one of
the pressing social problems of our ageing society. An esti-
mated 1.2 million people suffer from diseases of the central
nervous system in Germany today. Two-thirds of them are
Alzheimer's patients. Each year approximately 200,000 new
cases are diagnosed.
When Alzheimer examined samples of brain tissue from the
dead patient histologically he discovered numerous clumps
of protein that had led to the degeneration of the nerve cells.
Pathological protein deposits in the brain are also found in
patients with Parkinson's disease and Huntington's disease,
as well as in lesser known diseases such as corticobasal de-
generation (CBD), progressive supranuclear palsy (PSP), Pick's
disease and multiple system atrophy (MSA).
All these neurodegenerative diseases are referred to as pro-
teopathies and are to date incurable. Due to their specific
composition, the protein aggregates also serve as diagnostic
markers for characterising and differentiating the different
diseases. While with Alzheimer's disease it is mainly the nerve
cells (neurons) which transmit signals that are affected, with
other diseases the supportive cells (glial cells) of the brain are
also affected. For example in cases of MSA, typical half-moon
shaped or triangular deposits can be found in the glial cells
that cover the axons of nerve cells with an insulating protective
layer, the so-called oligodendrocytes.
In the "Molecular Neurobiology/Neurochemistry" research
group at the Department of Biology and Environmental Sci-
ences, we are examining the pathological changes in these
cells and the molecular causes underlying these changes.
MSA is a rapidly progressive neurodegenerative disease that
affects multiple systems and exhibits symptoms similar to
those in Parkinson's disease. Typical symptoms are slowed
movements, difficulties with balance and swallowing, speech
impairment and trembling. We are using rats andmice to stu-
dy the dynamic origins of the aggregates and the molecular
mechanisms. We make cell cultures from the brains of these
animals, which are then kept in incubators over long periods
of time and serve as model systems.
In several projects funded by the German Research Founda-
tion (DFG), we have collaborated intensely with researchers
at the University of Pennsylvania (USA), Aarhus University in
Denmark, the University of Göttingen and Klinikum Bremen.
Our most recent research, the results of which we reported
in several international science journals (e.g., PlosOne, Glia,
Journal of Neurochemistry), demonstrated that impaired
"
quality control" in the nervous system and a malfunction of
the systems involved in the degradation of proteins can con-
tribute to pathological processes. In our current research we
are examining the key question of whether the modulation
of autophagy, a cellular self-cleaning process, can be used as
a therapeutic measure to treat diseases of the brain and also
to regulate ageing processes.
In the course of evolution, cells have developed a strategy
for breaking down intra-cellular proteins or entire organelles
they no longer need into their individual components.
They "self-digest", so to speak, to make the products of this
decomposition available for metabolism again. This highly
efficient recycling process is called "autophagy" (Greek: to
eat oneself), or to be precise "macroautophagy". Autophagy
serves to maintain the inner balance of cells. It is a kind of
cleaning mechanism that removes and recycles defect or
deformed proteins and ageing organelles, or in other words
waste materials and cellular debris. Over-cleansing can lead
to cell death. On the other hand a disruption or weakening
of the autophagic mechanism can have fatal consequences
and contribute to the development of diseases such as cancer,
Parkinson's or Alzheimer's.
The term "autophagy" was coined by the Belgian researcher
Christian de Duve, who was awarded the Nobel Prize for
Medicine in 1974 for his seminal research in the field of bio-
Müllentsorgung durch Autophagie: Mitochondrien und andere
Zellbestandteile werden von einer Membran (rot) umhüllt, das
Autophagosom verschmilzt mit Lysosomen (Autolysosom) –
und die lysosomalen Enzyme (blau) zerlegen den Inhalt des
Autophagosoms.
Waste disposal via autophagy: mitochondria and other cell
components are enclosed in a membrane (red), the
autophagosome fuses with lysosomes (autolysosome) –
then the lysosomal enzymes (blue) break down the contents
of the autophagosome.
