An investigation into the lipid-binding properties of alpha-, beta- and gamma-synucleins in human brain and cerebrospinal fluid

Brain Res. 2007 Sep 19:1170:103-11. doi: 10.1016/j.brainres.2007.07.027. Epub 2007 Jul 20.

Abstract

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. alpha-Syn has biochemical properties and a structural motif characteristic of fatty acid binding proteins. Using the fatty acid binding resin Lipidex-1000, we investigated the capture of alpha-, beta-, and gamma-syn proteins as lipid-associated proteins from normal and DLB brain lysates, and from normal human cerebrospinal fluid (CSF). These were eluted from Lipidex-1000 and analyzed by SDS-NuPAGE followed by Western blotting. Using this methodology, we have been able to extract full-length and truncated forms of alpha-syn from brain lysates. We also extracted low levels of beta-syn from DLB brains, but failed to extract any gamma-syn. We were able to capture only full-length monomeric alpha-syn from normal human CSF. Our data confirm the fatty acid binding properties of alpha-syn, and to a lesser extent beta-syn, but suggest that gamma-syn does not share this same characteristic.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive / physiology*
  • Brain / metabolism*
  • Brain Chemistry / physiology*
  • Cerebrospinal Fluid / metabolism*
  • Dextrans / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Lewy Body Disease / metabolism
  • Lewy Body Disease / physiopathology
  • Membrane Lipids / metabolism*
  • Synucleins / metabolism*
  • alpha-Synuclein / metabolism
  • beta-Synuclein / metabolism
  • gamma-Synuclein / metabolism

Substances

  • Dextrans
  • Membrane Lipids
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
  • gamma-Synuclein
  • lipidex