$12.6 Million NIH Grant Will Advance Research on Aging and ALS, Other Neurodegenerative Diseases

A research team led by Northwestern University has been granted $12.6 million by the National Institute on Aging at the National Institutes of Health (NIH) to study the role of protein quality control in aging and neurodegenerative diseases such as Alzheimer’s and  amyotrophic lateral sclerosis (ALS).

The project brings together researchers at five U.S. institutions and will be known as the Proteostasis Institute.

Led by Richard I. Morimoto, PhD, biology professor and director at the Rice Institute for Biomedical Research in Northwestern’s Weinberg College of Arts and Sciences, the collaboration includes a team of scientists from Stanford University, Harvard Medical School, the University of California, San Francisco and The Scripps Research Institute.

“We have the ‘A-team’ on the mechanisms of protein quality control,” Morimoto said in a press release. “Together we can accomplish much more than a single lab could achieve.”

Researchers’ goal is to learn which molecular events increase the susceptibility for neurodegenerative diseases and other age-related diseases in older people.

Specifically, they will look into protein homeostasis, or proteostasis, the biological quality control processes that ensure proteins are made at the right levels and perform their correct function.

A protein lifecycle is a multi-step process that includes its production, its proper 3D folding, its transport to target sites (within or outside cells), and degradation.

Cells need to keep all these steps in check to maintain healthy proteins and, with that, keep overall health.

“As humans age, quality control of proteins declines,” Morimoto said.

“Our goal is to understand both how the cellular machinery functions in health and also how it fails in aging, increasing the risk for protein misfolding, aggregation and proteotoxicity. A priority will be to develop successful small molecule strategies to prevent and restore proteostasis in neurodegenerative diseases,” he said.

Morimoto is a recognized expert in protein homeostasis. He and his team at Northwestern identified the human heat shock genes, which instruct for the production of key players in protein homeostasis, known as molecular chaperones — proteins that assist in the correct folding and assembly of other proteins.  

The research team recently funded by the NIH will combine genetic model organisms such as yeast and Caenorhabditis elegans (a free-living roundworm), as well as mouse models of disease and patient-derived nerve cells, to identify the molecular events that accompany aging and underly neurodegenerative diseases including ALS, Alzheimer’s, Parkinson’s and Huntington’s disease.