The goal of this proposal is to investigate the role of lipid storage compartments in our cells, known as lipid droplets (LDs), within motor neurons, to understand how they contribute to the development of hereditary spastic paraplegia (HSP) — a group of inherited neurological disorders primarily characterized by stiffness and weakness in the legs. Symptoms of HSP can appear in childhood, often causing additional issues such as developmental delays and problems with intellectual abilities, which significantly affect quality of life. Recent evidence suggests that abnormal fat buildup in brain cells may be linked to HSP and motor function disorders. This is supported by the fact that mutations in certain genes involved in fat storage and utilization are known to cause HSP. However, we still do not fully understand why fat accumulates in the brain and what effects this abnormal buildup has on HSP symptoms.

In this study, we aim to uncover the role of fat and its breakdown in neuronal function, including its role in energy production and the formation of neuronal cell membranes. We also seek to understand how the shapes and functions of motor neurons are altered by abnormal fat accumulation in the brain. Ultimately, we hope to find ways to remove fats from the affected brain cells and determine whether clearing fat improves the motor defects seen in HSP patients.

Successful completion of this project will greatly advance our understanding of how fat and LD biology influence neuronal functions. It could potentially lead to new approaches for treating HSP patients, improving their physical abilities, mental well-being, and significantly improving the quality of life for children affected by these motor function disorders.