Parkinson’s disease (PD) is the second most common neurodegenerative disorder that is characterised by progressive loss of dopamine neurons and abnormal intra-neuronal accumulation of protein α-synuclein (αS). None of the available treatments have shown ability to slow down the progression of the neurodegeneration. One of the therapeutically potent approaches to combat PD is neurotrophic factor (NTF)-based therapies. Delivery of NTFs to the brain shows a notable therapeutic potential due to the ability to stop and reverse neurodegeneration in animal models. The most potent NTFs for PD therapy so far are CDNF and GDNF that have been recently studied in clinical trials on PD patients. Despite of the promising results, CDNF and GDNF does not pass through the blood brain barrier (BBB) and should be delivered to the brain through a risky microsurgery. Thus, there is a great need for an effective method that can deliver CDNF/GDNF through the BBB avoiding intracranial surgery. Another promising strategy for curing PD is based on αS clearance and control of its pathological aggregation and propagation. Our preliminary results showed that beta-casein coated AuNPs have great capacity to reduce αS aggregation and can be used to deliver NTFs to the brain. This proposal combines nanomedicine and molecular neurobiology to develop multi-functional AuNP-based medicine against PD that will positively impact the disease progression through mitigation of the parthenogenesis associated with αS and support the survival of dopamine neurons by CDNF/GDNF delivery to the brain. The applicant will get training needed for his future independent research career through hands-on training in the top scientific laboratories and by managing the highly innovative research at the interface of different disciplines connecting two excellent scientists: Prof. Saarma, a world leading molecular neurobiologist and Prof. Teesalu, an expert in homing peptides.
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