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Inhibiting the bioconversion of dynorphin fragments correlated to L-DOPA induced dyskinesia using on-tissue histochemistry and MALDI imaging mass spectrometry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2015 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Parkinson's Disease (PD) is a progressive neurodegenerative disease with an incidence of 1% at the age of 65 years which also is the average age of diagnosis. The cardinal motor symptoms of PD include rigidity, resting tremor, bradykinesia and postural instability. These symptoms are mainly due to cell death of neurons in the substantia nigra pars compacta, leading to a deficiency of the neurotransmitter dopamine. The medical treatment of Parkinson's disease consists of restoring this deficiency through ingestion of L-DOPA. However, the encouraging effects of L-DOPA therapy also introduced involuntary movements after long-term treatment, these adverse effects is referred to as L-DOPA induced dyskinesia (LID) and lowers the life quality of PD patients. It has been observed that an upregulation of the dynorphin B (DynB) precursor prodynorphin mRNA is occurring in LID.  The overexpression of dynorphins in L-DOPA treated rats may be causing LID by an imbalance in neurotransmission due to enzymatic activity on dynorphin neuropeptides. Hypothetically, this opens for a novel treatment of LID if the bioconversion of dynorphin fragments associated with dyskinesia is inhibited. Finding such an inhibitor would significantly improve the life quality of PD patients suffering from LID. The aim was to inhibit the bioconversion of DynB fragments correlated to LID using on-tissue histochemistry and MALDI IMS. This was done with both more general and specific enzyme inhibitors (opiorphin and phosphoramidon). Furthermore, a new method for studying enzyme activity on complete brain sections was developed by incorporating a chemical inkjet printer for substrate and matrix application.

Place, publisher, year, edition, pages
2015. , 30 p.
Keyword [en]
Dynorphin B, MALDI imaging mass spectrometry, enzyme inhibition, L-DOPA induced dyskinesia
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-274254OAI: oai:DiVA.org:uu-274254DiVA: diva2:896213
Subject / course
Educational program
Master of Science Programme in Pharmacy
Available from: 2016-10-06 Created: 2016-01-20 Last updated: 2016-10-06Bibliographically approved

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