Researcher Tunnels Deep into the Brain for the Root of Neurological Disorders
Srinivasa Subramaniam, Ph.D., likes to run. One day, he had a eureka moment when he stopped to hydrate. “What activity in his brain motivated his stopping?” he wondered.
That question inspired the research Subramaniam oversees in his lab, where he and his team investigate molecular interactions in Huntington’s disease (HD) and Parkinson’s disease (PD), two major neurological disorders that affect movement.
“Knowing on the molecular level what’s happening within cells and between different brain regions shows us the impact of these diseases and how these factors work together to propel them,” said Subramaniam, associate professor in the Department of Chemistry and Biochemistry at Florida Atlantic University’s Charles E. Schmidt College of Science and a member of the Stiles-Nicholson Brain Institute. After creating and experimenting with a novel mouse model, the team realized the classic explanation — that neurotransmitters motivate movement — did not address the full picture. Instead, their findings pointed to interactions between proteins in the striatum, a brain region critical to motor function.
Following that path, the team has made major breakthroughs in three different areas:
TUNNELING NANOTUBES
In 2022, Subramaniam published a study in Science Advances that a protein called Rhes builds strange structures, dubbed tunneling nanotubes, between cells. It uses the nanotubes to transport HD proteins, thereby spreading the disease throughout the brain. The team is currently developing methods to block the progression of HD by preventing Rhes from forming nanotubes.
STALLED RIBOSOMES
During normal physiology, structures called ribosomes translate the genetic language in mRNA into proteins. In 2021, Subramaniam published a study in Nature Communications that mutant Huntington mRNA stalls the ribosomes on the RNA strand, reducing protein production. The team is currently working on pharmacological inhibitors of a protein that is produced when the ribosomes are stalled — a mechanism that eliminated the disease in mouse models.
STRIATUM SIGNALING
Every aspect of movement depends on signaling between cells in the striatum. In 2020, Subramaniam published a study in Science Advances that the RasGRP1 protein regulates two critical signaling pathways in PD, causing strange movements in patients who take L Dopa. The team is currently studying the pathways and other regulatory proteins in greater detail.
Subramaniam said he hopes the team’s research will eventually lead to effective therapies for Huntington’s and Parkinson’s disease. “I’m excited that impacting tunneling nanotubes or ribosome dysfunction could be a way to treat these devastating conditions,” Subramaniam said.