2017-2018 Alzheimer’s and Related Diseases Research Award*

Developing an Expression Platform for Tetrameric Alpha-Synuclein to Advance Systemic Biochemical Studies

VCoA*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.


Developing an Expression Platform for Tetrameric Alpha-Synuclein to
Advance Systemic Biochemical Studies

Heather Lucas, PhD

Virginia Commonwealth University

The aggregation-prone protein α-synuclein (αS) has been linked to neurodegenerative diseases such as Alzheimer’s disease (AD) and, more commonly, to Parkinson’s disease and Lewy Body Dementia. This protein has been suggested as a modulator of cognitive function, yet its native function and diseaserelated conformation remain ill-defined. New findings have indicated the presence of a native tetrameric alpha-helical conformation that is stable to aggregation. A convenient method to isolate tetrameric αS for biochemical studies has yet to be reported, even though stabilization of this aggregation-resistant conformer may represent a viable therapeutic approach. Moreover, metal dyshomeostasis has long been linked to PD, but the influence of biometals on the aggregation propensity of tetrameric αS cannot be studied systematically until a robust method of accessing the tetramer is identified. Accordingly, an expression and purification platform will be developed for tetrameric αS that exploits fusion protein technology and relies on mild isolation techniques available through affinity chromatography, rather than conventional ion exchange chromatography methods that require high salt and dilute protein conditions. This platform will extend the reach of biochemical and biophysical investigations of αS, yielding valuable insight into a key protein that lies at the crossroads of several neurodegenerative diseases and setting the stage for the identification of new targets for drug development.

(Dr. Lucas may be contacted at 804/828-7512, hrlucas@vcu.edu)

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