Neurorestorative Properties of Cerebral Dopamine Neurotrophic Factor in Alpha Synuclein Pre Formed Fibril Model
Korpikoski, Jaan (2019)
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:amk-201905098924
https://urn.fi/URN:NBN:fi:amk-201905098924
Tiivistelmä
The diagnosis Parkinson’s disease is most commonly given at the age of 50 but the patient might have had the disease already for years.
The disease is commonly graded by the severity of the symptoms and how it limits normal life. The main brain regions of interest in Parkinson’s are striatum and substantia nigra. The latter has axonal connections to striatum with its dopaminergic neurons.
Lewy bodies (LBs) are thought as a hallmark in Parkinson’s disease. They are aggrega-tions from proteins. The main protein in the aggregates is called alpha synuclein (asyn). It is an abundant protein in neuronal cells. If the conformation of this protein is changed to a misfolded from through metabolic change called phosphorylation, it will acquire amyloid features. This means it will start to aggregate and turn other alpha synuclein proteins into the misfolded form. It has been shown that by injecting these misfolded proteins as pre formed fibrils (pff) of alpha synuclein it is possible to mimic the pathology of Lewy bodies in alpha synuclein.
Neurotrophic factors (NTFs) are small proteins that promote neuron survival and control the number of neurons in the nervous system. NTFS are promising candidates for treat-ment of PD. Cerebral dopamine neurotrophic factor (CDNF) is a novel trophic factor and it has earlier been shown to be neuroprotective and neurorestorative in mouse, rat and mon-key Parkinson animal models and is current in clinical phase I/II patient trials.
Aim of this thesis work was to study the neurorestorative properties of CDNF against the phosphorylation and spreading of misfolded alpha synuclein by injecting alfa synuclein fibrils to rat brain. After the pathology has formed, the animals were injected with CDNF in two different concentrations. After two weeks the brains were immunohistologically stained and LB were counted from striatal area of the brain. Results between groups werecompared and analyzed statistically.
The disease is commonly graded by the severity of the symptoms and how it limits normal life. The main brain regions of interest in Parkinson’s are striatum and substantia nigra. The latter has axonal connections to striatum with its dopaminergic neurons.
Lewy bodies (LBs) are thought as a hallmark in Parkinson’s disease. They are aggrega-tions from proteins. The main protein in the aggregates is called alpha synuclein (asyn). It is an abundant protein in neuronal cells. If the conformation of this protein is changed to a misfolded from through metabolic change called phosphorylation, it will acquire amyloid features. This means it will start to aggregate and turn other alpha synuclein proteins into the misfolded form. It has been shown that by injecting these misfolded proteins as pre formed fibrils (pff) of alpha synuclein it is possible to mimic the pathology of Lewy bodies in alpha synuclein.
Neurotrophic factors (NTFs) are small proteins that promote neuron survival and control the number of neurons in the nervous system. NTFS are promising candidates for treat-ment of PD. Cerebral dopamine neurotrophic factor (CDNF) is a novel trophic factor and it has earlier been shown to be neuroprotective and neurorestorative in mouse, rat and mon-key Parkinson animal models and is current in clinical phase I/II patient trials.
Aim of this thesis work was to study the neurorestorative properties of CDNF against the phosphorylation and spreading of misfolded alpha synuclein by injecting alfa synuclein fibrils to rat brain. After the pathology has formed, the animals were injected with CDNF in two different concentrations. After two weeks the brains were immunohistologically stained and LB were counted from striatal area of the brain. Results between groups werecompared and analyzed statistically.