Ph.D. Defence by Kenneth Kastaniegaard
Kenneth Kastaniegaard will defend his Ph.D. thesis on: "Biochemical model for the development of neurodegenerative diseases – The role of posttranslational modifications of proteins, extracellular vesi-cles and autoimmune development."
05.04.2019 kl. 13.00 - 13.00
The etiology and pathology of neurodegenerative diseases is vastly unknown. Neu-roinflammation is known to be involved and have been suggested to be a major driving force in the progression of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease and multiple sclerosis (MS). In MS treatment options are mainly immunomodulators targeting either T- or B-cells, which slows down disease progression, but no cure has been discovered. MS stands out from the prior mentioned diseases, as it has been suggested an autoimmune disease, because chronic inflammation plays a central role in the disease progression. Though autoim-munity is the most accepted hypothesis for disease introduction, new hypothesis also suggested primary oligodendrocyte dysfunction and malfunctional metabolisms as possible disease triggers.
In this thesis, we focus on using proteome analysis to elucidate relation between pro-tein expression patterns and disease development as well as mechanisms central for neurological health. Using the animal models; experimental autoimmune encephalo-myelitis and cuprizone, we investigate the central mechanisms; autoinflammation, de-myelination and remyelination. We also discuss, which multiple sclerosis related mechanisms is reflected in these models.
Using etomoxir, we also explored the effect of altering lipid metabolism on disease progression in the experimental autoimmune encephalomyelitis model.
This thesis also focusses on, how post translational modification of proteins is an es-sential process in cell signaling and how modifications can be associated with autoim-mune development as well as a possible connection between dysfunctional metabolism and the development of autoimmunity. Using state of the art mass spectrometry setups, we show that discovery-based protein post translational modification analysis is pos-sible and allows for a deeper proteome analysis. We also demonstrate how this can be used to monitor potential antigenic modification on proteins during disease and disease progression.
Fredrik Bajers Vej 7D2, room D2-106