Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
1836 The University of Texas at El Paso (143724)
Principal Investigator: Kirken,Robert A
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 380,000
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 6/8/22 - 2/29/24
Restricted Research: YES
Academic Discipline: Border Biomedical Research Ctr
Department, Center, School, or Institute: Border Biomedical Research Ctr
Title of Contract, Award, or Gift: 4-NONYLPHENOL AND THE MECHANISM OF ALZHEIMER’S DISEASE
Name of Granting or Contracting Agency/Entity:
NIH - NATL INST OF GEN MEDICAL SCIENCES
CFDA Link: HHS
93.307
Program Title:
Minority Health and Health Disparities Research
CFDA Linked: Minority Health and Health Disparities Research
Note:
Alzheimer's disease (AD) is a progressive brain disorder associated with continuous decline in thinking that leads to loss of behavioral, social, and cognitive skills. Aging is the most consistent risk factor in developing AD and recent evidence suggests that environmental factors play a significant role in this process. Recent studies show that environmental pollutants and chemicals can induce AD-like symptoms. Research from our laboratory demonstrates that 4-Nonylphenol (4-NP), an endocrine disrupting compound, and an environment pollutant, disrupts microtubules (MT) and alters the localization and expression of Tau. Tau protein and its phosphorylation status has been shown to be linked to the initiation and progression of AD and AD-related dementia. Earlier studies exhibited that 4-NP exposure produces learning and memory impairment in adult rats, and causes behavioral and cognitive deficits in offspring when exposed prenatally. Our preliminary studies indicate that 4-NP causes a substantial neuronal loss in the zebrafish embryos. Altogether, these results point towards the adverse effects of 4-NP on neuronal development, neurodegeneration, and learning/memory deficits. Therefore, our hypothesis is that long-term exposure of 4-NP can induce AD-like pathology and behavior by disrupting the cytoskeleton, and inducing tau hyperphorylation and protein aggregation. Both cell cultures and a zebrafish model will be used to conduct the study. We will test our hypothesis by addressing following two specific aims. In Aim-1, we will determine the mechanism of 4-NP-induced cytoskeletal disruption, and Tau hyperphosphorylation in a cell culture model. The goal of Aim-2 is to utilize the zebrafish model to study the effects of 4-NP on learning and memory deficits. It is anticipated that the proposed study will delineate the mechanism by which 4-NP induces AD and related dementia, which affect Hispanic population in US/Mexico border community disproportionately.
Discussion: No discussion notes