Multitarget drugs against prion diseases

March 21, 2011

The central nervous systems of humans and cattle alike are attacked by prions (abnormal insoluble amyloidogenic proteins) when they suffer from Creutzfeldt–Jakob disease (CJD) or bovine spongiform encephalopathy (BSE).

This causes a steady deterioration of neurological function and ultimately leads to death. There is no currently approved treatment for prion diseases, and no drug candidates are expected to enter clinical trials soon. In ChemMedChem, Maria Laura Bolognesi (University of Bologna, Italy) and colleagues argue in support of a multitarget drug discovery strategy as an alternative way to develop effective anti-prion agents.

Under the dominant drug discovery paradigm "one disease, one target, one molecule," which ignores the polyetiological nature of prion diseases and similar maladies, developing anti-prion therapies is a particular challenge; indeed, this paradigm could be a factor in the ongoing failure of current neurotherapeutic drugs.

Bolognesi and colleagues now describe the discovery of rationally designed molecules endowed with various activities relevant for combating prion neurodegeneration. A new series of chimeric molecules were generated by linking the antioxidant fragment of lipoic acid to heteroaromatic prion-recognition motifs. These compounds effectively counter both prion fibril formation and oxidative stress in a cell culture model of prion replication.

The reported in vitro results make these compounds effective candidates for further in vivo investigations into their multiple biological properties against prion diseases.

Explore further: Is there more to prion protein than mad cow disease?

More information: Maria Laura Bolognesi, Hybrid Lipoic Acid Derivatives to Attack Prion Disease on Multiple Fronts, ChemMedChem,

Related Stories

Is there more to prion protein than mad cow disease?

September 30, 2008

Prion protein, a form of protein that triggers BSE, is associated with other brain diseases in cattle, raising the possibility of a significant increase in the range of prion disease. Publishing their findings in the open ...

Mutant proteins result in infectious prion disease in mice

December 5, 2008

A worldwide group of scientists has created an infectious prion disease in a mouse model, in a step that may help unravel the mystery of this progressive disease that affects the nervous system in humans and animals. The ...

Sequence and structure key to prion disease transmission

June 14, 2010

Prion diseases are lethal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE; commonly known as mad cow disease) in cows. A team of researchers, led ...

New research focuses on prion diseases

March 14, 2011

New research by Chongsuk Ryou, researcher at the UK Sanders-Brown Center on Aging and professor of microbiology, immunology and molecular genetics in the UK College of Medicine, may shed light on possible treatments for prion ...

Recommended for you

A new form of real gold, almost as light as air

November 25, 2015

Researchers at ETH Zurich have created a new type of foam made of real gold. It is the lightest form ever produced of the precious metal: a thousand times lighter than its conventional form and yet it is nearly impossible ...

Getting under the skin of a medieval mystery

November 23, 2015

A simple PVC eraser has helped an international team of scientists led by bioarchaeologists at the University of York to resolve the mystery surrounding the tissue-thin parchment used by medieval scribes to produce the first ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.