A decade of work has culminated in researchers reconstructing a protein that is key to defending the brain against Parkinson’s disease.
Researchers at the University of Dundee have made a breakthrough by uncovering the 3D structure of an enzyme, PINK1, that can protect the brain against Parkinson’s disease. The disease is characterised by the degeneration of neurons, mainly in the motor system, causing symptoms such as tremors and difficulty walking. By knowing more about the protein, researchers now believe that they are in a far better position to therapeutically exploit its protective qualities.
Mutations in the gene encoding PINK1 have been identified in patients with early-onset Parkinson’s, which alerted researchers to it as a potential therapeutic target. PINK1 encodes a kinase enzyme that plays an important role in protecting brain cells against stress. Patients with mutated forms of the protein lose its protective effect is lost, leading to the degeneration of cells controlling movement that account for Parkinson’s symptoms.
Functional PINK1 deals with damaged mitochondria, targeting them for degradation with the help of two proteins, ubiquitin and parkin, which form part of the ubiquitin-proteasome system that degrades faulty proteins. The Scottish study has shed light on how PINK1 manages this, by spotting unique control elements that recruit ubiquitin and parkin. This explains why mutation of the enzyme can have such a devastating effect.
Dr Miratul Muqit, Wellcome Trust Senior Clinical Fellow and Consultant Neurologist explained the implications these findings could have on Parkinson’s therapies: “Solving the structure and workings of PINK1 gives us crucial insights into how it exerts a protective role in Parkinson’s… That knowledge can lead to the development of new drugs which could be designed to ‘switch on’ PINK1 to the benefit of patients with Parkinson’s.”
Regulatory bodies appear to be particularly tough when it comes to getting a drug targeting the CNS onto the market. But, Newron, one of our top 4 biotechs in Milan, managed it earlier this year with Xadago, which received approval to treat Parkinson’s. Swiss biotech, Prexton Therapeutics, has launched a Phase II trial to test whether its candidate can ease the motor symptoms of the condition.
The research represents a breakthrough in the molecular understanding of Parkinson’s disease, which had been lacking new approaches to treatment until Xadago entered the market earlier this year. The challenge now is to find a way to successfully target the protein therapeutically, perhaps, for example, in the form of gene therapy.
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