The 29th June 2019 saw us congregating for the 7th annual researchers meeting at Leicester University. We altered the format of the meeting as this time there was a theme that at least half of the speakers would be following. The themes were Dopaminergic neurons and Pluripotent stem cells and the meeting proved to be very informative.
Lia Panman opened proceedings followed by Flaviano Giorgini, Tilo Kunath, Miguel Martins, Liz Nash and finally Kirti Sharma. This snapshot below will focus on Miguel and there will be another 2 instalments to follow up with the other speakers being showcased.
Miguel not only co-organised the researchers meeting again but was also one of the speakers so here is Miguel Martins a Programme Leader at the MRC Toxicology Unit, now part of the University of Cambridge.
Miguel talked about his work using fruit flies as models to study Parkinson’s disease. He explained that some inherited forms of early onset Parkinson’s disease have typically been blamed on poorly functioning mitochondria (the ‘power stations within our cells).The endoplasmic reticulum, or ER, has the important job of ‘folding’ proteins so that they can carry out the vast majority of necessary functions within cells. Misfolded proteins are dangerous and cells often treat them as garbage, grinding protein production to a standstill if there are too many of them. While this system is protective, it also stalls the manufacture of vital proteins, and eventually, this kills neurons.
Miguel said that the interplay between poorly functioning mitochondria and ER stress might be at play in Parkinson’s. His team analysed flies with mutant forms of the pink1 or parkin genes. We already know these mutations starve neurons of energy by preventing the disposal of defective mitochondria. Mutations in Pink1 or parkin in humans cause some types of Parkinson’s disease.
Much like Parkinson’s patients, flies with either mutation move more slowly and have weakened muscles. The insects struggle to move. And, they lose dopaminergic neurons in
their brains – a classic feature of Parkinson’s. Compared to normal flies, Miguel’s team found that in these mutant flies defective mitochondria activate ER stress, and this ER stress kills dopaminergic neurons.
You can find the main conclusions of this study on this link to YouTube, here. Miguel’s team published the scientific study reporting these findings in Cell Death and Disease, a scientific journal. You can find the link to this study here.
Miguel also mentioned a followup study on this research, conducted on flies by a team in Belgium. This other study showed that contacts between mitochondria and the ER in flies with mutations in parkin or pink1 cause a lipid imbalance in a population of neurons that controls sleep. This affected their sleep patterns. Sleep problems are common in people with Parkinson’s. (If I may interrupt for a moment – it is true to say sleep is an almost universal problem for people with Parkinson’s – Lionel). Miguel mentioned that the sleep problems detected in flies might happen before their neurons die. It is therefore a possibility that problems with sleep might be an early (Bio) marker of this condition.