Stowers fellows and Stowers scientists—especially those at the interface of development and cancer—are deep into the cell-death dance. In particular, they study its role in neurodegenerative diseases such as Alzheimer’s. This is the focus of the research team led by biophysicist Randal Halfmann, who has initiated a study into how “death fold” proteins induce cellular self-destruction. They want to learn how these proteins are involved in killing brain cells in diseases characterized by misfolded proteins.
Douglas Green is a program leader at St. Jude Children’s Research Hospital, Memphis, Tennessee. He has spent the last several decades studying the cell death program. He emphasizes that while the concept of cell death may seem grim, it is a crucial process for maintaining overall health. Green states, “Cell death sounds morbid, but it’s essential for our health.”
Halfmann’s research looks at a specific group of cellular proteins that trigger cell death. He notes that this process requires a massive influx of energy. This calls into question whether its effects on brain health are largely positive, largely negative, or somewhere in between. His team’s thinking is that, in diseases such as Alzheimer’s, a misfolded protein called amyloid sets off the neurodegeneration. “That amyloid, for reasons we don’t really understand, ends up killing the neurons,” Halfmann explains.
The research team is currently exploring methods to inhibit cell death. Instead, they aim to create conditions that prevent toxic crystals from forming in the first place. Halfmann explains that all cells have built-in self-destruct buttons that you don’t want to accidentally push. “It just seemed like a really terrible way to live,” he states, highlighting the urgency of finding solutions to protect brain cells from unnecessary demise.
Green corroborates the significance of this research, noting that scientists are actively seeking treatments that can “modify or modulate the tendency of a cell to die.” He notes that a number of biotech companies are hard at work trying to inhibit particular pathways related to apoptosis, or programmed cell death. Twelve companies are committed to advancing antisense drugs. These drugs are able to prevent the synthesis of certain proteins, including those that induce cellular apoptosis, or programmed cell death.
The need for this research is highlighted by the increasing incidence of Alzheimer’s disease and other neurodegenerative diseases. Halfmann and Green’s findings certainly have interesting implications for therapeutic approaches. These approaches can protect brain function and prolong the health of neurons in people already affected by the disease.
Halfmann’s ultimate goal is straightforward: to keep brain cells alive longer and improve outcomes for those suffering from cognitive decline. Researchers and biotech companies are motivated by a crisis, a need for effective treatments with high unmet clinical need. Without a doubt, they are approaching this arena with fresh energy.
