RESEARCHERS from the University of Dundee have identified a potential new strategy for treating a range of neurodegenerative diseases and neurological disorders.
The research team led by Dr Satpal Virdee identified these potentials new treatments for brain diseases that have limited treatments.
The Virdee lab, in collaboration with colleagues at the University of Cambridge, have established the inner workings of an enzyme called MYCBP2 and shown how its activity promotes the self-destruction of axons after injury.
Their findings open the possibility of developing drugs that inhibit the enzyme’s activity, thereby providing therapies for diseases such as motor neurone disease, Parkinson’s and multiple sclerosis.
The team discovered in molecular detail how this unusual enzyme works.
They also showed for the first time that a pivotal catalytic step undertaken by MYCBP2 promotes neuron growth during early development, but also axon degeneration in response to nerve injury.
As nerve injury occurs in the early stages of many neurodegenerative diseases and after cancer therapy, blocking MYCBP2 enzyme activity might prove an effective strategy for treating a range of diseases and neuropathies.
Dr Satpal Virdee said: “Excitingly, the obtained structural and molecular insights might be leveraged to develop novel therapeutic agents thereby helping to address this unmet clinical need.
“Blocking an enzyme’s activity with a small molecule drug is a tried and tested strategy for treating disease. A problem with neurodegenerative diseases is that very few enzymes whose activity drives the degenerative process have been identified. Furthermore, the features of an enzyme that successfully engage a drug molecule are often shared by related enzymes.
“This makes it extremely challenging to develop specific drugs and is one of the reasons why many drugs have undesirable side effects. This study provides structural and molecular detail on the mechanism of MYCBP2 enzyme activity, while the seemingly unique mechanism of MYCBP2 should greatly facilitate the development of drugs that are highly specific against it.”
Dr Virdee’s team is based at the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit within Dundee’s School of Life Sciences. They were supported in this research by the Coleman lab at the John van Geest Centre for Brain Repair, Cambridge.
