Linking alpha-synuclein properties with oxidation: a hypothesis on a mechanism underling cellular aggregation.
α-Synuclein is a small, natively unstructured protein with propensity to aggregate. α-Synuclein fibrils are major components of Lewy bodies that are hallmarks of many neurodegenerative diseases. The solution properties and aggregation behavior of α-synuclein has been well characterized, but despite numerous studies that address the role of α-synuclein in cells, a clear physiological function of this protein remains a mystery. Over a hundred review articles of α-synuclein have been written in the last decade, making it difficult to list all of the important studies that have added to our insight of α-synuclein physiology. Instead, we briefly review the status of α-synuclein research and propose a model based on the idea that α-synuclein may not have an intrinsic activity in cells but rather, it modifies the function of a group of protein partners that in turn affect cell processes. We propose that it is the loss of its cellular partners under oxidative conditions that promotes α-synuclein aggregation accelerating neuronal death.
Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, 11794-8661, USA, suzanne.scarlata@stonybrook.edu.
Suzanne
S
Scarlata
Urszula
U
Golebiewska
D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010738:Type C Phospholipases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D010738:Type C Phospholipases