Untersuchung von Proteomveränderungen im Synaptosom von Patienten mit sporadischer Creutzfeldt-Jakob-Krankheit

Untersuchung von Proteomveränderungen im Synaptosom von Patienten mit sporadischer Creutzfeldt-Jakob-Krankheit

Misfolded Prion Form-specific Synaptic Proteome Alterations in sporadic Creutzfeldt-Jakob Disease

Martin Nowak

Doctoral thesis

Date of Examination: 2013-03-27

Date of issue: 2013-03-07

Advisor: Crozier, Thomas Prof. Dr. Dr.

Referee: Zerr, Inga Prof. Dr.

Referee: Dresbach, Thomas Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-000E-0B77-A

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Abstract

English

Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by wide clinical and pathological variability. This heterogeneity might be caused by the involvement of different molecular pathways depending on the prion agent type (or prion strain), which is thought to be determined by prion protein conformation. In these studies we show altered synaptic proteome patterns in MM1- and VV2-sCJD subtypes. Analysis of 2D maps revealed that 40 various protein spots were differentially expressed in sCJD in at least one sCJD subtype when compared to age-matched controls. Among them, 29 protein spots could be identified what corresponded to 23 different proteins. Surprisingly, only one protein displayed common dysregulation in both subtypes. However, a strong tendency to common dysregulation could be observed for another eight proteins. Remaining proteins displayed significant subtype-specific dysregulation. Interestingly, many prion-dysregulated proteins were identified that were previously associated with synaptic structure and activity, mitochondrial function and calcium metabolism or AD pathophysiology.

Keywords: Creutzfeldt; sporadic; synaptic; proteome

Schlagwörter: Creutzfeldt; sporadisch; Synaptosom; Proteom