PARP: targeting a cancer enzyme for disease modification in Parkinson’s
- Cancer enzyme affects Parkinson’s disease, Science: November 2, 2018.
- Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease, Science: November 2, 2018.
The takeaway
Why is it important?
%
IMPACT
- Novelty 80%
- Proximity 80%
- Deliverability 70%
Impact Opinion
“Prof Ted and Valina Dawson have been investigating the role of PARP in Parkinson’s for more than a decade, and their latest research report represents a major step forward in our understanding of how this protein may be involved in the condition. A really appealing aspect of the study is that clinically available PARP inhibitors have such a powerful effect in multiple models of PD. The idea of repurposing them for Parkinson’s, however, may be complicated by toxicity/safety and brain penetrance issues, which may be solvable with re-formulation. But this report is extremely encouraging research.”
Background
The details
To further test the role of PARP1 in dopamine neuron death, the researchers deleted the PARP gene and also inhibited PARP using two different PARP inhibitor drugs, in neuron cultures as well as mice. The result was a significant increase in neuron survival and a drop in PARP1 and PAR.
The researchers also looked at the postmortem brains of people with Parkinson’s and they found higher levels of PAR (compared to healthy control samples) in the region where the dopamine neurons reside. These results lead the researchers to conclude that PARP1 inhibitors should be further investigated for use in Parkinson’s.
Next steps
Further research, however, is needed into PAPR inhibitors, as well as their potential to be used in combination with other experimental disease modifying drugs such as exenatide, in efforts to reduce the toxic effects of misfolded alpha-synuclein on neurons as well as glia.
Related work
- Cancer enzyme affects Parkinson’s disease, Science: November 2, 2018.
- Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease, Science: November 2, 2018.