Scientists have utilized cutting-edge optical methodologies to investigate the creation of protein clusters that are implicated in neurodegenerative conditions. Through the examination of a protein related to ALS, the researchers have obtained unparalleled understanding into the shift of proteins from a liquid to a solid state, thereby illuminating our understanding of ailments like Alzheimer’s and ALS. Included is a nanometric scanning image illustrating protein condensate interactions. Acknowledgment: The University of Sydney.
Analyzing proteins at the nanometric scale provides valuable perspectives for the therapeutic approach to neurodegenerative disorders.
Numerous conditions that impact the brain and nervous system have been attributed to the accumulation of protein aggregates—specifically their transformation from liquid to solid states within cells—although comprehensive understanding of this phenomenon remains elusive.
The conversion from liquid to solid form can initiate the development of structures known as amyloid fibrils, which can subsequently generate plaques within neurons, thereby leading to neurodegenerative illnesses like Alzheimer’s.
In a collaborative effort, biomedical engineers from the University of Sydney, alongside scholars from the University of Cambridge and Harvard University, have developed innovative optical technologies for closely monitoring the aggregation process of these proteins.
By scrutinizing a protein linked to Amyotrophic Lateral Sclerosis (ALS)—a disease that afflicted renowned astrophysicist Professor Stephen Hawking—the researchers from Sydney meticulously observed the protein’s transition from its liquid phase to a solidified state.
A 3D confocal microscopy scan of FUS protein condensate, incubated for 24 hours, disclosed the unique core-shell structure unveiled through this study. Acknowledgment: The University of Sydney.
“This represents a monumental advancement in fundamentally understanding the genesis of neurodegenerative conditions,” stated Dr. Yi Shen, the principal author of the study, which was published in the Proceedings of the National Academy of Sciences (PNAS) in the United States.
“We are now equipped to observe these pivotal protein transitions from liquid to solid at a nanometric scale—a scale a million times smaller than a meter,” commented Dr. Daniele Vigolo, a Senior Lecturer in the School of Biomedical Engineering and an affiliate of the University of Sydney Nano Institute.
Although proteins commonly undergo phase separation from liquid to liquid during crucial and benign biological functions—such as human embryogenesis, which facilitates essential biochemical reactions and promotes healthy protein interactions—this mechanism also elevates the likelihood of malfunctioning aggregation.
“Dysfunctional aggregation creates unhealthy protein clusters in human cells, resulting in aberrant structures connected to neurodegenerative disorders, as these proteins can no longer swiftly revert back to their liquid state,” explained Dr. Shen, who is also an ARC DECRA Fellow at the School of Chemical and Biomolecular Engineering and a member of Sydney Nano.
“This emphasizes the importance of scrutinizing the dynamics of condensates, as they have a direct influence on pathological states,” she added.
For the first time, the team’s nanoscale optical observations have established that the protein’s transition from liquid to solid initiates at the surface interface of the protein condensates, and revealed heterogeneous internal structures within these protein clusters, challenging the previously held assumption that they were homogeneous.
Dr. Vigolo concluded, “Our discoveries hold the potential to significantly enhance our fundamental comprehension of neurodegenerative diseases, thereby opening up a promising new domain of research aimed at elucidating the mechanisms behind Alzheimer’s and ALS, which affect millions globally.”
The research was financially supported by various organizations including the Frances and Augustus Newman Foundation, the Wellcome Trust, the European Research Council, the US Alzheimer Association, ALS Canada-Brain Canada, the Canadian Institutes of Health Research, and the National Institute on Aging.
Reference: The original study was published on 7 August 2023, in the Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2301366120.
Frequently Asked Questions (FAQs) about Neurodegenerative Diseases
What is the main focus of this research study?
The main focus of this research study is to understand the formation of protein aggregates associated with neurodegenerative diseases like Alzheimer’s and ALS. The researchers utilized advanced optical techniques to closely
