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Seeking cures for terrible brain diseases

Diseases of the brain: progressive conditions affect the body and mind in different ways.

Diseases of the brain: progressive conditions affect the body and mind in different ways.

Proteins are the biological workhorses of the cell responsible for crucial processes that sustain life. To become functionally active, a protein molecule must fold into a complex and precise three-dimensional structure. However, the folding process is not fool-proof and misfolded proteins that escape the stringent quality-control systems of the cell could be trapped as a partly folded intermediate, or could interact with other molecules forming aggregates. A gain of new toxic activities from aggregated species can have dire consequences, as is observed in multiple neurodegenerative diseases that share the pathological feature of deposition of insoluble aggregates.

Various studies have linked both Alzheimer’s and Parkinson’s diseases to the build-up and deposition of specific proteins in the brain. Toxic protein clumps extensively damage nerve cells and cause symptoms like dementia in Alzheimer’s disease (AD), or difficulty in movement in Parkinson’s disease (PD). Degenerative diseases of the brain afflict tens of millions of people around the world. With increased life expectancy, the number of cases are rising rapidly worldwide, meaning that such maladies pose major health and economic burdens on societies. Yet, no therapies are available that are able to prevent, or slow down, the inexorable decline in brain function.

In our current research project, which is being funded by a grant awarded by the University of Malta, we address the question of whether the rogue protein aggregates selectively target mitochondria, the energy-generating powerhouses of brain cells, causing dysfunction of mitochondria and triggering neuronal cell death. We explore precisely how mitochondria can be made more resistant to insult by these aggregates, for instance by using small-molecule compounds as mitochondrial-protectants to preserve the permeability barrier of mitochondria. These re-energised mitochondria would be able to withstand damage by the harmful protein deposits and hence prevent, or slow down, neurodegeneration. The current project concept has emerged from the past eight years of intensive research work in our laboratory on the causes of neurodegeneration at the molecular level. Our ambition is that it will drive research and innovation into developing new strategies for the treatment of AD and PD.

Our research group, led by Professor Neville Vassallo at the University of Malta and the Centre for Molecular Medicine and Biobanking, has also joined other major international research groups focused on drug discovery in brain neurodegenerative disorders. In particular, we are collaborating closely with the Ludwig-Maximilians-University of Munich and the Max Planck Institute for Biophysical Chemistry in Göttingen, both in Germany, on new medicines. A compound called ‘anle138b’ improved memory function in a mouse model of Alzheimer pathology, and the data suggest that therapeutic effects are expected to be achieved in Alzheimer patients with oral administration of anle138b. Previous research had shown that anle138b also holds promise for treatment of Parkinson’s disease patients. Although the results are very encouraging, the drug’s effectiveness now has to be demonstrated in humans.

Dr Angelique Camilleri is a Postdoctoral Fellow at the Centre for Molecular Medicine and Biobanking, University of Malta.

Did you know?

• The ocean is 3,682.2 metres deep on average. That is about eight Empire State Buildings, stacked one on top of the other. The deepest part of the ocean, however, is about 11,030 m feet down. That is roughly like 25 Empire State Buildings.

• Pugs’ cute little flat faces are the result of a genetic mutation.

• There are extraterrestrial dust particles on your rooftop. They are called micrometeorites and are about 400 microns in size.

• You think this is hot? On Sept. 13, 1922, the mercury soared to 57.8 degrees Celsius in El Azizia, Libya. Scientists say this is the hottest temperature ever recorded on the planet, though higher temperatures might have occurred in places where there are no measuring stations.

• Prosopagnosia is a disorder in which people struggle to recognise faces.

For more trivia see: www.um.edu.mt/think

Sound bites

• Earth scientists exploring how ocean chemistry has evolved found similarities between an event 55 million years ago and current predicted trajectories of planet temperatures, with regards to inputs of carbon dioxide into the atmosphere and oxygen levels in the oceans. As the oceans warm, oxygen decreases while hydrogen sulfide increases, making the oceans toxic and putting marine species at risk.

https://www.sciencedaily.com/releases/2018/08/180801115226.htm

• Blue diamonds – like the world-famous Hope Diamond at the National Museum of Natural History – formed up to four times deeper in the Earth’s mantle than most other diamonds, according to new work. The so-called Type IIb diamonds owe their blue colour to the element boron, an element that is mostly found on the Earth’s surface. But an analysis of the trapped mineral grains in 46 blue diamonds examined over two years indicate that they crystallised in rocks that only exist under the extreme pressure and temperature conditions of the Earth’s lower mantle.

https://www.sciencedaily.com/releases/2018/08/180801131610.htm

To find out some more interesting science news, tune in Radju Malta on Saturday Mornings at 11.05 am and listen to “Radio Mocha”

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