Richard Parsons

Dr Parsons' research focuses upon the role that toxicology has in pathogenic process in neurodegenerative disease, in particular the interplay between environmental exposure and genetic susceptibility.

Alzheimer's disease – the production of amyloid-ß by the sequential actions of ß- and ß-secretase, and its subsequent aggregation into senile plaques, is one of the hallmarks of Alzheimer’s disease (AD).

Dr Parsons' research has investigated how protein lipidation (palmitoylation and isoprenylation) regulates the protein:protein interactions between ß-secretase (BACE1) and other proteins involved in its subcellular trafficking. BACE1 undergoes highly-regulated subcellular trafficking within the cell, and within certain subcellular regions BACE1 associates with its substrate, APP, leading to cleavage and production of amyloid-ß.

Dr Parsons' research has shown that inhibition of these protein lipidation reactions results in altered subcellular trafficking and reduced amyloid-ß. In collaboration with colleagues from St. George's, University of London, he is currently investigating the role that protein isoprenylation has in the amyloid-ß-induced inflammatory response. 

Parkinson's disease - dysfunctional energy metabolism is present in many neurodegenerative diseases, which arises from reduced Complex I activity. The highly oxidising environment within the dopaminergic neurones of the substantia nigra, the neurones which degenerate in Parkinson's, leaves them particularly susceptible to reduced Complex I activity.

Dr Parsons is interested into how N-methylation biotransformation of proneurotoxins is involved in the pathogenic process. His research has shown that the enzyme nicotinamide N-methyltransferase (NNMT), which converts nicotinamide (a form of vitamin B3) into 1-methylnicotinamide, is significantly higher in PD brain than in disease-control brain. This appears to be a neuroprotective response of the cell to the underlying pathogenic process, as 1-methylnicotinamde is neuroprotective towards dopaminergic neurones, increasing Complex I activity and stabilising its structure.

Also, overexpressing NNMT in a dopaminergic neuronal cell-line leads to increased cell viability and Complex I activity. In collaboration with colleagues both within the Division and at Imperial, the next stage in Dr Parsons' research is to design lead compounds which exploit this neuroprotective action of 1-methylnicotinamide, which may provide a viable therapeutic avenue for the treatment of PD