Grants and Contracts Details
Description
Traumatic brain injury (TBI) causes neuronal damage followed by neurodegeneration and cognitive deficit. However, there is no effective Food and drug administration (FDA)-approved drug for the treatment of TBI. Compelling experimental data from our group and others demonstrate that oxidative stress and mitochondrial dysfunction are linked to neuropathological sequelae of TBI. Identifying molecular targets which may protect mitochondria, improve mitochondrial biogenesis/bioenergetics, and decrease oxidative stress is of great importance to combat TBI and neurodegenerative diseases. Although evidence suggests that low-density lipoprotein receptor-related protein (LRP1) plays an important role in cell proliferation, migration, and energy homeostasis, and responds to cellular stress conditions like oxidative stress, hypoxia, tissue injury, and inflammation, how LRP1 regulates mitochondrial function and ROS is not known. Brain mitostasis and mitochondrial energy metabolism recognized as critical regulator of neuronal health and survival. Acute and chronic oxidative stress negatively regulates mitochondrial dynamics and function that become detrimental to cell survival. Our evidence demonstrates that LRP1 deficiency protects mitochondrial function and mitostasis from oxidative stress by stimulating pathways related to mitochondrial biogenesis and antioxidants. Hence, here we hypothesize that neuronal LRP1 deficiency in the adult mouse brain will improve mitostasis and mitochondrial dysfunction by mitigating oxidative stress-mediated cellular damage following TBI.
Status | Finished |
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Effective start/end date | 9/26/23 → 9/30/24 |
Funding
- University of Kentucky Neuroscience Research Priority Area: $25,000.00
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