| |
| author |
Jose Fabrizzio Cevallos
| | title |
Modulating Neurotrophin P75 Receptor to Protect Neurons from an Alzheimer's Disease Cell Culture System through the use of LM11A-31
| | abstract |
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that impairs
memory, cognitive judgment, and other behaviors (Cass 2017). It is the leading cause of
dementia in late adult life in the United States and is associated with a significant social burden
and increased morbidity and mortality in the elderly (Cass 2017). Currently, 47 million of people
live with dementia globally, and it is estimated to reach 131 million in the next decades (Tiwari
et al 2019). Previous research has reinforced the possibility that the neurotrophin P75 receptor is
directly responsible for the degeneration and generation of forebrain cholinergic neurons in
Alzheimer's disease, therefore, its modulation could be an extraordinary therapeutic target
(Coulson et al 2009). Other studies identified a collection of non-peptide small molecules with
selected structural and physical chemical features suggested to interact P75, and that has been
shown, in in vitro studies, to inhibit Aβ-induced degeneration in a P75 dependent manner
(Simmons et al. 2014). Here, we examined the hypothesis that modulating the P75 receptor with
LMA11-31 can protect neurons from degeneration through mechanisms of microtubule stability,
healthier mitochondria, and reduction of oxidative stress in a cell culture system. MTS assays
were used to measure neuron viability. In this experiment, it was determined that cell viability
was higher in the presence of (FAB/NMDA) and LMA11-31 compared to other conditions, such
as FAB/NMDA, and Growth Media alone. To measure oxidative stress generated in
mitochondria, MitoSox Red Mitochondrial superoxide indicator assays were conducted.
Superoxide experiments were inconclusive as levels of oxidative stress did not change from all
conditions. To observe the number of mitochondria that had healthier electrical potential in the
presence of LMA11-31 JC-1 Mitochondria Membrane Potential Assays were conducted in the
presence of (FAB/NMDA) and LMA11-31. To visualize cell morphology, fluorescence
microscopy, Immunocytochemistry (ICC) was used, showing an increase of microtubule stability
relative to the control in the (FAB/NMDA) and LMA11-31 condition. Investigating whether
modulation of the P75 receptor would prevent degeneration in different conditions that may be
occurring in Alzheimer's disease represents an incredible opportunity to study a possible drug
therapy against Alzheimer's disease.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2022)
|
| advisor |
Dr. Roger Knowles
|
| committee |
Dr. Sam Kongsamut
Dr. Stephen Dunaway
|
| full text | JCevallos.pdf - requires Drew uLogin |
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