It was believed Parkinson’s occurs when mitochondria – which supply power to cells – malfunctioned, causing brain cells that produce the key hormone dopamine to die.
But Leicester University researchers found most of the problem related to another part of the cell, called the endoplasmic reticulum (ER)
In a study with fruit flies that had been genetically modified to develop Parkinson’s, the scientists managed to at least partially correct the problem so that the number of brain cells increased and the flies’ muscles remained healthy.
Cell Death and Disease - Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson’s disease
“By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration.
“While the finding so far only applies to fruit flies, we believe further research could find that a similar intervention in people might help treat certain forms of Parkinson’s.”
Parkinson’s, which affects about 127,000 people in the UK, causes shaking, memory and speech problems, anxiety and depression among other symptoms.
There was also a five-year study by an international team led from the University of Leicester has found a way of ‘reversing’ symptoms of neurodegenerative diseases such as Parkinson’s and Alzheimer’s – using fruit flies as test subjects.
The researchers have demonstrated that genetic and pharmacological approaches can be used to lower levels of toxic metabolites in the nervous system and thereby alleviate several symptoms of neurodegeneration.
Mutations in PINK1 and PARKIN cause early-onset Parkinson’s disease (PD), thought to be due to mitochondrial toxicity. Here, we show that in Drosophila pink1 and parkin mutants, defective mitochondria also give rise to endoplasmic reticulum (ER) stress signalling, specifically to the activation of the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response (UPR). We show that enhanced ER stress signalling in pink1 and parkin mutants is mediated by mitofusin bridges, which occur between defective mitochondria and the ER. Reducing mitofusin contacts with the ER is neuroprotective, through suppression of PERK signalling, while mitochondrial dysfunction remains unchanged. Further, both genetic inhibition of dPerk-dependent ER stress signalling and pharmacological inhibition using the PERK inhibitor GSK2606414 were neuroprotective in both pink1 and parkin mutants. We conclude that activation of ER stress by defective mitochondria is neurotoxic in pink1 and parkin flies and that the reduction of this signalling is neuroprotective, independently of defective mitochondria.
SOURCES - Cell Death and Disease, Independent UK, Leicester University