Resource | Mollie's Blog No 6
Meet the Scientists
A very exciting two weeks. Since writing my last blog I have been let loose on my main project for the year – what a nice surprise! I am really pleased to be getting underway with the project prior to Christmas as this gives me a few weeks to do some groundwork so that I can hit the ground running in the new year. As I am quite sure many people are feeling… roll on 2021.
So, what is my main project?
A paper published on the 3rd August this year has potentially identified a new gene that may be causative of early onset Parkinson’s Disease. This gene has the very catchy name of PPP2R5D. PPP2R5D is one of three subunits that make up the characteristic structure of an enzyme known as Protein Phosphatase 2, or PP2A.
The role of PP2A is to remove phosphate tags from substrates, acting much like a pair of scissors by cutting the bonds between the phosphate tag and the substrate it is attached to. This mechanism is involved in a whole host of pathways in the cell but of particular interest here, is its involvement in the pathways that control function and maintenance of neurons (the cells that make up our brains). PP2A is composed of a catalytic subunit, this is the part that mediates the enzymes action, a regulatory subunit, this is what PPP2R5D is and its job is to guide PP2A to where it needs to be in the cell and control what substrates the enzyme acts on. Thirdly, there is a scaffolding subunit, which holds it all together forming the active enzyme.
Until recently, mutations in PP2A have been associated with a very rare neurodevelopmental disorder. People with these mutations have moderate to severe intellectual disability, autism, speech impairments, hypotonia (low level of muscle tone leading to ‘floppiness’), macrocephaly (overly large head) and many other medical complications such as epilepsy or endocrine and cardiac abnormalities. In the paper published in August, researchers identified 3 cases in which patients with a mutation in PPP2R5D also developed early onset Parkinson’s (between the ages of 22 and 40).
A key feature of the pathology of the brains of these patients is that, unlike some forms of Parkinson’s, there are no Lewy bodies found. Lewy bodies are abnormal build-ups/aggregation of protein in the brain, this can cause damage to brain cells leading to dementia, this may be referred to as Parkinson’s dementia. What is significant about this absence of Lewy bodies in the cases studied in this paper is that this is reminiscent of the pathology of Parkinson’s Disease that is associated with a mutation in the Parkin gene – a key gene in our lab. This has led us to hypothesize that the PPP2R5D protein may somehow be involved in the same pathways as the Parkin protein.
I will be trying to prove whether there is a genetic link between mutations in PPP2R5D and Parkinson’s Disease. This could be a hugely exciting finding. If mutations in this gene turn out to be causative of Parkinson’s Disease it will expand our knowledge of the mechanisms that cause Parkinson’s and will add another potential target or biomarker for the diagnosis and treatment of Parkinson’s in the future.
I am incredibly excited to get stuck into this project and feel very privileged to have been given the opportunity to undertake this investigation. I really look forward to keeping you updated with my work and the rest of the cutting-edge research coming out of the lab.