Mariana Pehar

Position title: Assistant Professor

Email: mapehar@medicine.wisc.edu

Phone: (608) 265-8140

DEPTARTMENT:

Medicine

EDUCATION:

Ph.D. in Neuroscience, Universidad de la República, Uruguay

RESEARCH DESCRIPTION:

The main goal of Dr. Pehar’s research program is to understand the molecular mechanisms linking aging to the development of neurodegeneration, with the aim to identify new therapeutic targets for the prevention and treatment of neurodegenerative diseases. In particular, Dr. Pehar’s lab focuses on understanding the role of neurotrophin signaling in the progression of neurodegenerative process. Neurotrophins have the ability to promote either survival or death, depending on the cell type considered and physiological context. During aging and pathological conditions, the increased production or decreased clearance of free radicals leads to oxidative stress and post-translational modification of signaling proteins such as neurotrophins. Dr. Pehar’s group identified a new mechanism by which the ability of neurotrophins to induce cell death is regulated by post-translational oxidative modifications. Post-translational modified neurotrophins induce neuronal death and affect the communication between neurons and other cells of the nervous system, including astrocytes. Astrocytes are essential for proper neuronal function and altered crosstalk between astrocytes and neurons has a pivotal role in the progression of neurodegenerative processes. Dr. Pehar’s research is seeking to better understand the signaling pathways activated by oxidatively modified neurotrophins in order to identify new therapeutic targets for the treatment of age-related neurodegenerative diseases. Current Projects: 1) Neurotoxicity of oxidatively modified NGF in neurodegenerative diseases. The lab is elucidating the mechanism by which oxidative stress increases the pro-death signaling of neurotrophins and its pathophysiological relevance in models of neurodegeneration. The main goal is to identify targets for therapeutic intervention. 2) Molecular mechanisms of astrocyte-mediated neurotoxicity in aging and disease. Astrocytes play an active role in neurodegenerative processes. This research project focuses on elucidating the mechanisms by which astrocytes promote neuronal death in neurodegenerative conditions. The overall goal is to develop neuroprotective therapeutic strategies using astrocytes as the main target.

KEY WORDS:

Aging, astrocytes, neurodegeneration, neurotrophins, oxidative stress

Link to Publications