“Decoding the Chemistry Behind Alzheimer’s Disease Therapies”

Speaker: Michael R. Nichols, Ph.D. Professor, Department of Chemistry & Biochemistry, Director of the biochemistry and biotechnology program, University of Missouri-St. Louis, President of the American Society for Neurochemistry

Date: Wednesday, August 14, 2024, noon-1 p.m.

Locations:

• UMSL Millennium Student Center, The Chamber (lunch is provided for the first 50 attendees)
• MU NextGen Building, Atkins Seminar Room (lunch is provided for the first 50 attendees)
• Or join via Zoom
   

 Register Here

Description

Alzheimer’s disease is the sixth leading cause of death in both Missouri and the broader U.S. A recent report found that the number of Missourians living with Alzheimer’s will exceed 130,000 by 2025, and over 11 million Americans report caring for a friend or loved one with AD. Not everyone will get the condition and it’s clear there are genetic factors at play, but identifying its precise causes remains one of the world’s great scientific challenges.

In the past few years, the FDA has approved new drugs that represent an important step forward by targeting the pathophysiology of the disease rather than the symptoms alone. Unfortunately, these drugs can only slow the process of cognitive decline.

Dr. Michael Nichols at the University of Missouri-St. Louis is helping to push this field forward by focusing on the biochemistry of Alzheimer’s. His lab targets the amyloid beta (Aβ) protein, which is known to initiate the disease by depositing in the brain, and their studies focus on Aβ-stimulated inflammation pathways. 

Protein aggregation and accumulation is a key aspect of Alzheimer’s disease

The aggregation and accumulation of amyloid beta protein (Aβ) is widely considered to be the cause of Alzheimer’s disease (AD), while aggregated tau protein is associated with the clinical manifestations of AD. The two proteins are the most outstanding pathological features of the disease and can be observed as fiber/filament-like structures in the brain as senile plaques (Aβ) and neurofibrillary tangles (tau). A longstanding effort in my laboratory has been to define the conditions that influence Aβ aggregation and identify the biophysical features that trigger biological activity. A major part of this has been to study formation of soluble aggregation intermediates and their properties. We have discovered over the course of many years that Aβ42 protofibrils have numerous unique properties that encourage interactions with immune cells. The overall data indicates Aβ42 protofibrils readily interact with, and are rapidly taken up, by brain immune cells. Furthermore, Aβ42 protofibrils trigger early and robust inflammation via cell-surface receptors and intracellular pathways. Those, and additional findings, demonstrate numerous mechanisms by which Aβ42 directly interacts with immune cells of the brain. In two separate additional projects, we have developed a sensitive and selective antibody to Aβ42 protofibrils and, are further exploring the details of Aβ42-stimulated inflammation. The rationale is to better understand how Aβ42 creates a toxic inflammatory environment in the brain during the course of AD.

About the Speaker

Dr. Michael R. Nichols is a Professor in the University of Missouri-St. Louis (UMSL) Chemistry & Biochemistry Department and the Director of the UMSL Biochemistry & Biotechnology Program. He also currently serves as President of the American Society for Neurochemistry. He earned a BS in Chemistry from Lindenwood College and a PhD in Chemistry & Biochemistry at Purdue University. Following a postdoctoral fellowship in the Department of Neuroscience at Mayo Clinic Jacksonville, he began his career at UMSL in the Fall of 2004. His research focuses on the biochemistry of Alzheimer’s disease (AD). Specifically, he researches the biophysics of the amyloid-β protein (Aβ) and the mechanisms by which Aβ impacts immune cells and inflammatory pathways.

The Discovery Series

The NextGen Precision Health Discovery Series provides learning opportunities for UM System faculty and staff across disciplines, the statewide community and our other partners to learn about the scope of precision health research and identify potential collaborative opportunities. The series consists of monthly lectures geared toward a broad multidisciplinary audience so all can participate and appreciate the spectrum of precision health efforts. 

For questions about this event or any others in the Discovery Series, please reach out to Veronica Lemme at lemmev@health.missouri.edu.