Rice Chemistry chair Martí discusses role in brain health, impact of Prop 14

Angel Martí, chair of Rice University’s Department of Chemistry, is leading efforts to highlight chemistry’s role in advancing brain health research. With Texas voters set to decide on Proposition 14 in November, which would create the Dementia Prevention and Research Institute of Texas (DPRIT), Martí says now is the right time to underscore how fundamental science paves the way for breakthroughs in treating Alzheimer’s, Parkinson’s and related disorders.

In a Q&A with Rice News, Martí discussed how Rice scientists are uncovering the molecular mechanisms of neurodegenerative diseases, the significance of chemistry in developing therapies and how state investment could accelerate discoveries throughout Texas’ medical ecosystem.

Q: How is Rice’s chemistry department contributing to brain health research, and what role does your lab play in that effort?

A: The chemistry department plays a crucial role in neuroscience with several faculty members actively engaged in neurochemistry research. For instance, theoretical physicist Peter Wolynes is a world-recognized leader in computational methods to predict protein folding kinetics and structure. His research sheds light on why certain proteins and peptides associated with diseases are more susceptible to aggregation and amyloid formation.

Chemistry professor Han Xiao’s research group is developing probes that can cross the blood-brain barrier, essential for imaging and potential treatments. Chemistry professor Pernilla Wittung-Stafshede is studying how metals such as copper interact with amyloid proteins and their role in Alzheimer’s and Parkinson’s diseases.

In my lab, we focus on both pathogenic and functional amyloids. We investigate how proteins transition from folded to misfolded states, how oxidation affects their behavior and how these changes can lead to toxicity. These insights help clarify the harmful and beneficial roles of amyloids in the body.

Q: Your group studies the molecular structures of amyloids linked to Alzheimer’s and Parkinson’s. What has chemistry revealed that other fields might miss?

A: Chemistry reveals processes at the molecular level. Amyloids are challenging to study due to their insolubility and structural disorder. Standard techniques often fall short. By using light-induced footprinting and probes, we can map binding sites and comprehend how molecules interact with amyloids.

This is important because amyloid plaques in the brain are never isolated; they absorb metals and molecules, altering their properties. If such binding results in toxicity, we can design molecules that displace the harmful components. These fundamental chemical questions are essential in drug design.

Q: You’ve developed probes and sensors that detect amyloid formation. How do these tools move us closer to effective treatments?

A: Traditional imaging can take hours, but photochemical probes enable us to observe amyloid aggregation in real time. They also uncover how molecules bind to amyloid aggregates, which is crucial for drug design. For instance, we can analyze how oxidation relates to amyloid aggregation stability. These insights allow us to develop strategies for modulating toxicity or engineering drugs that target amyloids more effectively.

Q: Why is basic science, including uncovering binding sites, critical for developing therapies for neurodegenerative diseases?

A:  It is difficult to create effective treatments if we don’t understand what’s happening at the molecular level. Many neurodegenerative diseases involve complex protein misfolding and aggregation events. By identifying the chemical triggers, we can ultimately design interventions that address the root causes rather than just the symptoms.

Q: What makes amyloid diseases particularly challenging?

A: Once proteins aggregate into insoluble fibrils, the brain’s natural clearance systems struggle to remove them. These plaques then absorb metals, sugars and a variety of other molecules, which lead to oxidation and trigger immune responses, making them stable and difficult to reverse. Chemistry is at the heart of understanding and tackling this complexity. 

Q: How would Proposition 14 impact Rice’s research in brain health?

A: It would be transformative. Texas has become a global leader in cancer research through the Cancer Prevention and Research Institute of Texas. DPRIT could achieve similar success for neurodegenerative diseases. It would establish infrastructure, fund research and attract talent to the Texas Medical Center.

Q: If Proposition 14 passes, what opportunities do you see for translating your lab’s basic discoveries into clinical strategies for Alzheimer’s and Parkinson’s?

A: It would open a door for our chemistry researchers and for researchers across Texas.

It would enable us to expand programs, acquire advanced instrumentation and recruit top researchers. Collaborations between Rice and the Texas Medical Center would facilitate the translation of fundamental discoveries into clinical applications.

Q: Any final thoughts?
A: Proposition 14 offers a chance to revolutionize our approach to dementia and brain health. We’ve witnessed how state investment has been effective in cancer research. Now we can apply that successful model to neurodegenerative diseases. This initiative is not only about increasing lifespan but also about preserving the quality of life as people age.