Role of Nlrs in neurodegenerative diseases (New)

Nlrx1, belongs to NLR family of intracellular sensors that regulate mayor cellular pathway including cell death and inflammation. Previous research implicated Nlrx1 in regulation of autophagy and reactive oxygen species production during viral infection. In addition most recent publication implicated Nlrx1 in regulation of the cell death in fibroblasts cultures. Our preliminary data show that Nlrx1-/- mice are more prone to develop experimental autoimmune encephalomyelitis. The increased susceptibility of the Nlrx1-/- mice is associated with increased (2 fold) inflammatory infiltrate and induced astrogliosis (2 fold) compared to WT control. We also noted a drastic reduction (7 fold) in neuronal content in the spinal cords of Nlrx1-/- compared to WT mice. Such profound differences in the neuronal content cannot be explained by magnitude of the inflammatory response. Therefore, the cell death phenomenon that we observed has to be neuron specific.
Aim 1 is to characterize inflammation-induced cell death in primary cultures from WT and Nlrx1-/-mice.
Hypothesis: Nlrx1 inhibits inflammation-induced neuronal death. We will study inflammation-induced cell death in the mixed brain cultures that contain neurons, astrocytes, and microglia. In addition we will use oxygen/glucose deprivation model of stroke to screen several drag candidates. We will assess cell death by immunohistochemistry, flow cytometry, and Western blotting.
The results of these studies will lay foundation for development of new therapeutical agents to treat neurodegenerative diseases

Faculty Supervisor:

Denis Gris

Student:

Emilia Gonzalez Avila

Partner:

Discipline:

Medicine

Sector:

University:

Program:

Globalink