Grant: Project Grant

Oligodendrocytes (OLs) are a cell type in the central nervous system (CNS) that wrap the long processes extending from nerve cells (i.e. axons) in a fatty, membranous sheath called myelin. Myelin insulates the axon, protecting nerve cells and ensuring fast, efficient signaling. Thus, proper myelination of axons is critical for coordinated movement and cognitive functions (such as memory). The myelinating ability of OLs is essential to prevent CNS degeneration, and to promote repair from injury or under pathological conditions, but the efficiency of OL remyelination declines with age. This age-related impairment of remyelination is relevant to cognitive impairments accompanying several neurological disorders, including multiple sclerosis, Alzheimer's disease and dementia, Parkinson's disease and Huntington's disease. Little is known about the genes that govern myelin stability and repair in the aging CNS. The goal of our research is to determine how myelination and remyelination is affected by age-related alterations in gene networks. We will study how specific factors interact to regulate the expression of OL genes and proteins that are important for efficient remyelination of axons. Based on our previous studies, we hypothesize that two transcription factors (Hoxd1 and Nkx2.2) and a deacetylase enzyme (SIRT2) play important roles in controlling the progression of OLs from immature cells to mature cells that have assembled a myelin sheath. Establishing how specific factors regulate this process is important for understanding how to overcome the age-related decline in the ability of OLs to myelinate / remyelinate the axons of nerve cells. This research is the groundwork for developing therapeutic approaches to reverse CNS damage caused by several age-related neurodegenerative diseases.