Prof. Neville Vassallo, MD PhD, associate professor in neurochemistry and neurophysiology at the University of Malta’s Faculty of Medicine and Surgery, flips through images on his laptop of brain samples from patients who had Alzheimer’s dementia or Parkinson’s disease – two of the most debilitating and increasingly common neurological conditions.
“This is what amyloid deposits in the brain of individuals with Alzheimer’s and Parkinson’s diseases look like,” he says, pointing to widespread blue-stained deposits that had accumulated inside and outside of brain cells.
Amyloid deposits are formed when proteins misbehave, and start clumping together to form aggregates that are highly toxic to neurons. “Our quest is to gain a deeper understanding of the likely origins and consequences of this pathological behaviour by amyloid proteins,” says Vassallo.
Indeed, this – in a nutshell – is what the latest publication by Vassallo and co-workers is about, published in Nature’s Scientific Reports on October 20, 2020.
In their laboratory located at the University of Malta’s Centre for Molecular Medicine & Biobanking, Vassallo’s team generated harmful aggregates of a bacterial amyloid protein, known as HypF-N.
They then studied the effects these amyloid aggregates had on mitochondria isolated directly from neuronal cells. Mitochondria, due to their central role in energy generation, are often referred to as the neuronal cell’s “powerhouses”.
In fact, the UM researchers observed significant damage to mitochondria by HypF-N aggregates which conformed to a specific amyloid structure. Furthermore, they showed that the toxic aggregates created tiny, nanometer-sized holes in mitochondrial surfaces, which cause leakage of their contents.
“What is particularly intriguing”, points out Prof. Vassallo, “is that HypF-N, being a native bacterial protein, is not associated with any specific human neurodegenerative disease – meaning that we may have uncovered a common mechanism that is shared by amyloid proteins in general, and which may actually underlie various neurodegenerative disorders.”
Advances in understanding amyloids could lead to a powerful new class of medicines for the treatment of Alzheimer’s and Parkinson’s diseases.
Research in Prof. Vassallo’s laboratory was conducted by Maria Ylenia Farrugia, Dr Mario Caruana, Dr Stephanie Ghio and Dr Angelique Camilleri.
Other study co-authors include Prof. Claude Farrugia and Dr Ruben J. Cauchi of the University of Malta, together with Sara Cappelli and Prof. Fabrizio Chiti from the Department of Clinical Biomedical Sciences of the University of Florence, Italy.
This project was supported financially by the Faculty of Medicine & Surgery (University of Malta) and the Endeavour Scholarship Scheme (Malta). A grant from the A.X. Foundation, through the University’s RIDT, helped cover publication costs.
The full article can be freely accessed online through the Springer Nature SharedIt initiative.