Ubiquitinated IL-1β & Defective Inflammasome Formation in Alzheimer's Disease: Implications for Chronic Brain Inflammation
Abstract
Chronic inflammation, a prolonged and more long-term process, has been implicated in various diseases, including Alzheimer's. Alzheimer's is the most common form of progressive dementia, associated with memory deficits and neuron damage. Multiple hypotheses have been proposed for the development of the disease, and among them, chronic inflammation is increasingly considered as an important underlying factor for the disease's development.
This research explores the role of interleukin-1 beta (IL-1β), a key inflammatory cytokine, in Alzheimer's pathogenesis. Elevated IL-1β levels are found in the cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) patients. The study focuses on the post-translational modification of IL-1β specifically—ubiquitination, an enzymatic process involving the addition of ubiquitin molecules to a protein’s lysine residues, which acts as a signal leading to protein degradation and terminating cytokine signaling effects. It was hypothesized that abnormal ubiquitination of IL-1β in Alzheimer’s patients may lead to unchecked inflammation, accelerating neurodegeneration.
Using Western blotting, the amount of cleaved and ubiquitinated forms of IL-1β in postmortem brain tissues from Alzheimer’s patients and age-matched non-demented individuals were analyzed. Results indicate that Alzheimer's patients exhibit abnormal post-translational modification of IL-1β, varying accumulation of ubiquitinated IL-1β, and inconsistent presence of the inflammasome. These findings underscore the complexity of Alzheimer's inflammatory response and suggest novel areas of research that may help us identify potential targets for modulation to reduce Alzheimer’s risk.
Faculty Sponsors
Dr. Mohammad Golam Sabbir
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Ubiquitinated IL-1β & Defective Inflammasome Formation in Alzheimer's Disease: Implications for Chronic Brain Inflammation
Alvin Sherman Library
Chronic inflammation, a prolonged and more long-term process, has been implicated in various diseases, including Alzheimer's. Alzheimer's is the most common form of progressive dementia, associated with memory deficits and neuron damage. Multiple hypotheses have been proposed for the development of the disease, and among them, chronic inflammation is increasingly considered as an important underlying factor for the disease's development.
This research explores the role of interleukin-1 beta (IL-1β), a key inflammatory cytokine, in Alzheimer's pathogenesis. Elevated IL-1β levels are found in the cerebrospinal fluid and brain tissue of Alzheimer's disease (AD) patients. The study focuses on the post-translational modification of IL-1β specifically—ubiquitination, an enzymatic process involving the addition of ubiquitin molecules to a protein’s lysine residues, which acts as a signal leading to protein degradation and terminating cytokine signaling effects. It was hypothesized that abnormal ubiquitination of IL-1β in Alzheimer’s patients may lead to unchecked inflammation, accelerating neurodegeneration.
Using Western blotting, the amount of cleaved and ubiquitinated forms of IL-1β in postmortem brain tissues from Alzheimer’s patients and age-matched non-demented individuals were analyzed. Results indicate that Alzheimer's patients exhibit abnormal post-translational modification of IL-1β, varying accumulation of ubiquitinated IL-1β, and inconsistent presence of the inflammasome. These findings underscore the complexity of Alzheimer's inflammatory response and suggest novel areas of research that may help us identify potential targets for modulation to reduce Alzheimer’s risk.
