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Exploring neurodegeneration in Parkinson's disease

The mechanisms underlying Parkinson's disease (PD) are generally poorly understood. A recent EU-funded project investigated aspects of the neurodegeneration associated with the disease.
Exploring neurodegeneration in Parkinson's disease
PD is a common neurodegenerative disorder affecting about four million people worldwide. It not only alters individuals' quality of life, but also places a high economic burden on society. The disease is characterised by a progressive loss of brain neurons that release the dopamine (DA) hormone. The exact mechanism of this degeneration is unknown, and there is currently no treatment available to prevent or delay disease progression. Researchers explored some of these mechanisms in a project called MODIFYPD.

Previous studies on PD showed that selective neuron death could result from a pathogenic interaction between alpha-synuclein (alpha-syn), a brain protein, and DA. The first aim of MODIFYPD was to test in vivo whether increasing and inhibiting DA synthesis lead to increased and reverse alpha-syn toxicity and degeneration, respectively. Within a mouse model, they found that although DA levels increased the susceptibility to alpha-syn toxicity, it is not the main contributing factor under normal physiological levels.

Another potential cause of neurodegeneration is a chemical alteration (phosphorylation) of an alpha-syn amino acid, Ser129. The MODIFYPD study showed that increased levels of phosphorylated alpha-syn leads to alterations in DA handling. This may indirectly, or in combination with other factors, affect alpha-syn pathology.

These findings have contributed to an enhanced understanding of the mechanisms underlying neurodegeneration in PD. This could assist future researchers in the development of novel therapies for PD.

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