Neurodegenerative diseases cast a shadow of uncertainty over the lives of millions as neurons progressively fade away, leaving behind a trail of functional decline. Dr. Bradley R. Kraemer from the Department of Biological Sciences in the College of Science at The University of Alabama in Huntsville (UAH) seeks to unveil the intricate molecular underpinnings that govern these debilitating conditions. Many disorders, including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis (ALS), are linked to neurodegeneration. The fundamental questions that drive Dr. Kraemer's research are: what causes these neurons to perish, and can we manipulate the molecular interactions that underlie this deterioration to prevent their demise?
Dr. Kraemer's recent focus has turned to a family of growth factors – tiny messengers cells employ to communicate. These factors orchestrate cellular functions such as growth, survival, and migration. "These molecules are generally considered healthy for cellular function, but there is a diversity of these molecules, and they can have really complicated interactions; they can change due to different diseases," Kraemer says.
At the heart of this intricate process lies a critical protein: the p75 neurotrophin receptor. Positioned on the surface of cellular plasma membranes, its activation serves as a determinant, directing specific cells toward survival while directing the death of others. Its commands vary based on the cellular context and location within the body. This protein is particularly interesting in Parkinson's disease, "in individuals with Parkinson's disease; there is a population of neurons that communicate using the neurotransmitter dopamine, and those neurons progressively die. This leads to a lot of motor impairments," Kraemer says. These vulnerable neurons, known as dopaminergic neurons of the substantia nigra, express the enigmatic p75NTR protein. However, the protein's role in this domain remains largely unexplored.
Drawing upon insights from diverse neuron types, where p75NTR has been associated with both promoting survival and orchestrating death, Dr. Kraemer assures that this protein occupies a central role in dictating the fate of dopaminergic neurons. The research develops through meticulous experimentation, utilizing cell culture models of Parkinson's disease and mouse models. Cells grown in Petri dishes are manipulated to emulate the injuries associated with Parkinson's disease, while surgical procedures in mice mimic the disease itself. The results are striking – the conditions that mimic Parkinson's activate p75NTR, hinting at its involvement in the disease.
Some questions emerge: What does the p75NTR do when activated? Is it promoting death by blocking signaling cascades, or is it an advocate for survival? Could boosting its signaling potentially shield Parkinson's patients from neuronal death? Dr. Kraemer's lab team embarks on a journey to decipher these mysteries. Recent studies involve treating cells with a p75NTR modulating drug, tilting its function toward pro-survival pathways and protecting dopaminergic cells from death. This breakthrough corroborates the critical role of p75NTR in governing cell survival.
Dr. Kraemer's interest in the connection between developmental pathways and later-life disorders grew as he delved deeper. During his graduate studies, he uncovered p75NTR's role in prompting neuronal death in segments of the sympathetic nervous system, which handles stress responses. As he advanced to a faculty role, he explored other nervous system areas where p75NTR's significance might extend. The activation of p75NTR due to injuries reminiscent of those seen in Parkinson's disease heightened his curiosity, leading him to consider Parkinson's disease as a possible context where the protein has a significant role.
Dr. Bradley R. Kraemer alongside students from the College of Science within his research laboratory.
A cornerstone of this pursuit lies in Dr. Kraemer's lab students. These active participants fuel the lab's engine of discovery. Undergraduate and graduate students take the lead by designing experiments, conducting assays, analyzing data, and charting future inquiries. With an open invitation to UAH's vibrant student community, Dr. Kraemer oversees the influx of eager inquiries, choosing those whose potential shines the most.
Ultimately, Dr. Kraemer's work carries profound implications for our understanding of neurodegenerative diseases. Through meticulous research and boundless curiosity, he desires to light the way toward new therapeutic avenues, bringing hope to those who face the shadows of these debilitating conditions.
