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EINBLICKE
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Cells continually
renew their contents.
chemistry and his discovery of lysosomes. Lysosomes are tiny
compartments consisting of a membrane that is filled with
special enzymes called acid hydrolases whose function is the
intracellular digestion or degradation of proteins, lipids, sugar
molecules and nucleic acids. Their task is to break down com-
plex macromolecules into sim-
ple components that can then
be released by the lysosomes
and used for reconstructing
newmacromolecules. Lysosomes are therefore also common-
ly referred to as "recycling units". They play a key role in the
autophagic process.
In early images made using the electron microscope, resear-
chers discovered tiny vesicles consisting of amembranewhich
contained cytoplasmic components and even entire orga-
nelles such as mitochondria, the power plants that supply our
cells with energy. Since then the steps that lead to the break-
down of cytoplasmic components and cellular organelles have
been thoroughly investigated. First a double-layered memb-
rane (phagophore) is formed, which expands and encloses
parts of the cytoplasm and organelles. This process produces
an autophagosome. Then the autophagosomes fuse with the
lysosomes, resulting in the formation of what are known as
autolysosomes. In autolysosomes, the components are broken
down, or "digested", with the help of lysosomal enzymes and
the recyclable material is released into the cytoplasm. In this
way cells continually renew their contents and free themselves
of unwanted, damaged components. Autophagosomes are
continually at work but multiply in stress situations, such as
when there is a lack of nutrients or in the presence of harmful
external influences.
In addition to lysosomal degradation, proteins can also be
broken down by a different system, the so-called proteasome.
In particular short-lived cytoplasmic proteins are disposed of
in this way. Frequently referred to as "waste bins", proteasomes
consist of many different protein units that are assembled
into a barrel-like structure. Large clumps of protein, however,
cannot pass through the entrance to the barrel and must
therefore be degraded by lysosomal digestion processes.
Consequently autophagy is the only process by which large
substrates such as protein clumps and organelles can be bro-
ken down. The two processes, waste disposal via lysosomes
and via proteasomes, are carried out in close communication
with each other. If the one process is blocked, the other can
potentially take over.
Cellular quality control through autophagy is especially im-
portant in the nervous system. Because nerve cells no longer
divide, the ballast of misfolded, useless proteins and damaged
or aged organelles such as mitochondria can no longer be "di-
luted" via distribution among daughter cells after cell division.
The hypothesis is that impaired waste disposal mechanisms
lead to the formation of protein clumps (amyloid plaques) in
brain cells which then clog up cells, hamper cellular processes
and trigger cell death.
There are indications from different research groups that
impaired autophagy, for instance a weakened self-digestive
system, plays a role in pathological processes in the brain. In
mice whose autophagic processes have been switched off,
neuronal degeneration processes and the formation of protein
aggregates have been observed.
The brains of Alzheimer's patients
exhibit an increased incidence of
autophagosomes. It is suspected
that although these vacuoles multiply at a higher rate than
usual, their fusion with the lysosomes, and consequently
digestion, is impaired.
Our research group was recently able to demonstrate that
protein deposits in the brains of MSA patients contain com-
ponents that are indicative of impaired autophagic processes.
In a cell culture model we were also able to induce protein
deposits similar to those found in living organisms. By stimu-
lating autophagy wewere subsequently able to remove these
deposits, thus simulating the cellular survival strategy.
In the past 25 years enormous advances have enabled us to
gain an extensive understanding of themolecular and clinical
fundamentals of neurodegenerative diseases. Nevertheless,
the possibility of a cure remains elusive. However research
activities across the globe hold out the hope that in the
coming years therapies can be developed to prevent or cure
these diseases.
Die Autorin
The author
Prof. Dr. Christiane Richter-Landsberg ist seit 1993 Hochschullehrerin
für „Molekulare Neurobiologie“ in Oldenburg. Sie studierte Phar-
mazie in Marburg und promovierte im Fach Biologie in Göttingen.
Nach Studienaufenthalten in Israel und USA habilitierte sie sich
1988
in Bremen. Ihr Forschungsinteresse gilt Nervenzellen und
Glia, Stressantworten und der Bedeutung von Stressproteinen in
Gehirnzellen.
Prof. Dr. Christiane Richter-Landsberg has been a lecturer in "mole-
cular neurobiology" at Oldenburg since 1993. She studied pharma-
ceutical sciences in Marburg and received her PhD in biology from
Göttingen. Following research visits to Israel and the US, in 1988 she
earned her habilitation in Bremen. The main focuses of her research
are neurones and glial cells, as well as stress responses and the role
played by stress proteins in brain cells.
Autophagy is an efficient
recycling process.
