Biology of nerve cell death during the course of neurodegenerative disease.

Current Lab PI - Dr. Fulin Ma

Current work involves the investigation of the role of aging in the onset and progression of Alzheimer's disease. DNA damage is a major driver of the aging process and therefore forms a key focus of our research. DNA damage in mature oligodendrocytes triggers their re-entrance into a cell cycle. As these normally postmitotic cells cannot divide, they go on to die. This leads to regression of myelination and directly leads to cognitive impairment, which accounts for a portion of the cognitive symptoms of different neurodegenerative diseases. In microglia, DNA damage causes fragments of the cells' own DNA to leak into their cytoplasm. Once there, the cell mistakes these fragments for an invading DNA virus and mounts an inflammatory response that includes release of neurotoxic substances into the environment. In neurons DNA damage also triggers an unscheduled cell cycle. As with oligodendrocytes the mature neuron cannot divide. Rather than die directly, however, the neuronal attempt at cell division initiates a program of cell senescence. Senescent neurons function poorly in their electrophysiological functions and also adopt a senescence associated secretory phenotype. The secreted substances add to the inflammatory profile during the disease process and thus exacerbate (and may initiate) the neurodegenerative sequence of events.

The work includes a strong translational interest that directs our studies towards a few select human neurodegenerative diseases including Alzheimer’s, a very common late-life dementia, and ataxia-telangiectasia, a very rare multisystem disorder of childhood.