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Neurodegenerative diseases and the protein quality control

10 October 2011

PhD ceremony: Mr. K. Seidel, 12.45 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertation: Neurodegenerative diseases and the protein quality control

Promotor(s): prof. H.H. Kampinga

Faculty: Medical Sciences

With increasing life-expectancy in the western world, diseases of old age are becoming more prevalent, in particular the neurodegenerative diseases. Here, certain components of the brain and spinal cord degenerate progressively. The symptoms are grave and have a severe impact on the patient’s lifespan and quality of life.

Some of these diseases occur sporadically without known cause (idiopathic), others are due to genetic risk factors or specific mutations. Many display a similar phenomenon: the aggregation of disease typical protein into microscopically visible lumps (aggregates), usually situated within neurons. The exact link from aggregating protein to neuronal cell death remains unresolved. Several systems are being studied for involvement in the disease processes. One of these is the Protein Quality Control (PQC), which clears old, and combats aggregated and aberrant proteins.

This thesis approaches the subject of neurodegenerative diseases from 2 angles. Part one is dedicated to the degenerative processes and protein aggregates. Here, the degeneration of the auditory system and a novel type of protein aggregation, as well as the high similarity of a genetic form of Parkinson’s disease to the idiopathic form is described. Part two concerns the response of the PQC in relation to protein aggregation. These data demonstrate that aggregation in neurodegenerative processes may ”escape” from the attention of the normal stress-regulated PQC system. They also demonstrate the existence of a stress response in astrocytes in degenerating areas, suggesting that upregulation of PQC systems in astrocytes may be important in combating neurodegeneration.

Last modified:15 September 2017 3.41 p.m.

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