Structures Behind the Amyloid Aggregation of alpha-Synuclein: An NMR Based Approach

MARIA L. ORCELLET; CLAUDIO O. FERNANDEZ

CURRENT PROTEIN AND PEPTIDE SCIENCE

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2011 vol. 12 p. 188 - 204

1389-2037

The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Evidence that alpha-synuclein amyloidogenesis plays a causative role in the development of Parkinson’s disease is furnished by a variety of genetic, neuropathological and biochemical studies. There is a major interest in understanding the structural and toxicity features of the various species populated along the aggregation pathway of this protein. The development of multidimensional Nuclear Magnetic Resonance (NMR) spectroscopy in liquid and solid state over the last decade has significantly increased the scope of molecules that are amenable for structural studies. The aim of this review is to provide a picture of how NMR tools were used in concert to decipher the structural and dynamic properties of the intrinsically disordered protein alpha- synuclein in its native, oligomeric, fibril and membrane-bound states. Understanding the structural and molecular basis behind the aggregation pathway of alpha-synuclein is key to advance in the design of a therapeutic strategy.