Uncovering new mechanisms of neurodegenerative diseases

Neurodegenerative disorders like Parkinson’s and Alzheimer’s have been stubbornly resistant to treatment. Only one new medication has been approved for Alzheimer’s, for instance, in more than a decade. In researching their root cause, Dr. William Flavin found that misfolded proteins that characterize these diseases spread throughout the brain in much the same way that infectious pathogens invade cells. View Halo Profile >>

Tell us about your research…

My research focuses on the prion-like propagation of neurodegenerative disease-related proteins such as alpha-synuclein, tau, and polyglutamine-expanded huntingtin. I determined that amyloid assemblies of these proteins invade target cells through endocytic vesicle rupture, in a similar fashion to cellular infection by some viruses and bacteria.

My research focuses on the prion-like propagation of neurodegenerative disease-related proteins such as alpha-synuclein, tau and polyglutamine-expanded huntingtin.

Utilizing fixed and live-cell immunofluorescent microscopic techniques to visualize these processes at the subcellular level, I further elucidated factors such as serine-129 phosphorylation and assembly strain conformation that dictate the potency of vesicle rupture, and showed that this process negatively affects lysosomal and autophagic degradation and may contribute to the formation of intracellular proteinaceous inclusions such as Lewy bodies.

Can you explain that to a non-scientist?

Numerous neurodegenerative diseases such as Parkinson’s, Alzheimer’s, ALS, and Huntington’s disease stem from aggregation of misfolded proteins and dysfunction in the cellular machinery meant to degrade these faulty protein deposits. New research has now established that protein aggregates from these various neurodegenerative diseases are capable of spreading between cells and to distant brain regions, a process which underlies the progressive and incurable nature of these diseases.

New research has now established that protein aggregates from these various neurodegenerative diseases are capable of spreading between cells and to distant brain regions, a process which underlies the progressive and incurable nature of these diseases.

My research determined the mechanism by which protein aggregates invade target cells, occurring in a very similar manner to viral or bacterial infection, and demonstrated that this damaging process of cellular invasion induces further dysfunction in cellular degradative machinery. Ultimately, my work contributed to a better understanding of the causes of neurodegenerative disease, and will help to design targeted, disease-modifying therapies in the future.

My research determined the mechanism by which protein aggregates invade target cells, occurring in a very similar manner to viral or bacterial infection, and demonstrated that this damaging process of cellular invasion induces further dysfunction in cellular degradative machinery

How could it someday impact patient lives?

The research and development of new therapeutics depends on a robust understanding of disease pathogenesis. Progress in treating Alzheimer’s, Parkinson’s, ALS, and many other neurodegenerative diseases has been limited by how little is known about the causes of these diseases. My work brought about an increased understanding of the mechanism for how misfolded protein aggregates can damage individual cells and spread from one cell to the next. This knowledge will allow future therapies to be designed which take this process into account and can intervene to slow or perhaps prevent disease progression.

This knowledge will allow future therapies to be designed which take this process into account and can intervene to slow or perhaps prevent disease progression.