Tag: disease

Novel drug molecule to treat Parkinson’s disease in young patients

Novel drug molecule to treat Parkinson’s disease in young patients

More than 100,000 Canadians currently live with Parkinson’s disease. A novel drug molecule being studied by researchers from McGill University could reactivate housekeeping functions in brain cells of young Parkinson’s patients, paving the way for potential future treatments for this incurable, degenerative disease.

“We are excited about this drug compound because it raises the possibility of a cure for Parkinson’s disease for a subset of patients,” said Kalle Gehring, a biochemistry professor at McGill University.

Developed by the biotech company Biogen, the new compound has shown promising results activating parkin, a key protein in the brain responsible for “cleaning up” and recycling damaged mitochondria – the energy powerhouse of the cell. When parkin doesn’t work properly, these damaged mitochondria accumulate, leading eventually to Parkinson’s disease.

In studies published in 2013 and 2018, Gehring shed light on the functions of parkin based on data collected at the Canadian Light Source (CLS) at the University of Saskatchewan (USask).

In this new follow-up study, Gehring used the CMCF beamline at the CLS to determine how the Biogen compound activates parkin. They found that it glues together parkin and a natural activator present in the cell. This molecular-level information is essential for the drug’s future development.

“The way the drug molecule turns on parkin is through a secondary route, which is effective for specific mutations of parkin that occur in younger patients,” he said.

After turning proteins into tiny crystals, Gehring and his team used a technique called protein crystallography to identify their 3D structures and learn where the novel drug binds and how it affects the proteins. The results are published in the journal Nature Communications.

“We need quality data to solve the protein structures and see their 3D pictures. It takes a facility like the CLS to take Canadian research to an international level,” said Gehring.

Read more on CLS website

A closer look at how cells package DNA

A closer look at how cells package DNA

Cryo-imaging reveals how cells efficiently store the genome

Our cells use an ensemble of histone proteins to fold and package the DNA genome into the nucleus. Histones also determine whether to expose DNA to enzymes to allow processes like gene expression, replication, and repair to occur. Although many in vitro studies have explored the mechanism histones use to fold and package DNA into higher-order structures called chromatin, less is known about chromatin organisation inside the nucleus of intact cells, and understanding this phenomenon could be key to understanding multiple DNA-associated processes. Recent advances in cryo-electron tomography have enabled scientists to observe these structures within the nucleus of rapidly cryopreserved cells. Reporting in Nature Communications, scientists at the University of Oxford collaborated with the electron Bio-Imaging Centre (eBIC) at the Diamond Light Source to capture chromatin in the nucleus of immune T cells, revealing that DNA is folded into more flexible and heterogenous fibres than previously modelled. Their experiments lay the groundwork for future studies into the roles of chromatin in health and disease.

Packing the essentials

Have you ever rushed to pack clothes into a suitcase and skipped the folding step only to find the suitcase wouldn’t close? Though it may have been a struggle, it doesn’t compare to the challenge our cells face when they pack 2 metres of DNA into a nucleus 200,000 times smaller in width. Here an efficient folding mechanism is key, and histone proteins direct the operation.

A complex of histone proteins act as a spool around which 147 base pairs of DNA can wind like thread. Multiple histone spools called nucleosomes can be found along the length of a DNA molecule and coil its strands into so-called chromatin. When chromatin is purified and observed using electron microscopy, scientists have observed that nucleosomes are spaced apart at regular intervals like beads on a string. These beads can then cluster together to form thicker chromatin fibres that pack the DNA into an even smaller volume.

Beyond efficiently folding DNA to fit inside the nucleus, histones play vital roles in regulating gene expression, DNA replication, and repair by loosening or tightening their grip on DNA and controlling its exposure to enzymes. An in-depth understanding of the folding mechanism could help researchers understand how chromatin affects multiple processes within the nucleus.

Read more on the Diamond website