| Popis: |
Alpha-synuclein (AS) is an intrinsically disordered protein mainly found in the presynaptic terminals of neurons1. The neuronal accumulation of AS amyloid aggregates, the formation of Lewy bodies, and axonal transport deficits are linked neuropathologically to amyloid disorders, called synucleopathies, including Parkinson's disease (PD)2,3. Though the exact mechanism causing PD is unclear, the sequestration of numerous proteins by intra-cellular amyloids has been suggested to play a role in the toxicity of amyloid diseases4. The abundance of cytoskeletal proteins in axons triggers the idea that amyloid formation may affect the organization and functional role of the cytoskeleton and thereby, neuronal function. We therefore investigated the binding of cytoskeleton (associated) proteins to AS monomers or amyloid aggregates in vitro. AS amyloid aggregates sequestered and immobilized various cytoskeleton (associated) proteins such as tubulins, actins, tau, kinesins and more. Furthermore, many of these proteins possess low micromolar affinity for AS monomers and fibrils. The binding of AS therefore slightly affected the functional assembly and physical properties of a few of the cytoskeletal proteins and networks. Unraveling the molecular details of binding and the disruptive interactions with AS would provide further insights into disease mechanism of PD.1) Fortin D. L. et al. J Neurosci. 25, 10913-21 (2005).2) Shults C. W. PNAS 103, 1661-68 (2006).3) Larsen E. C & Holzbaur E. L. F. BBA 1762, 1094- 08 (2006).4) Olzscha H., et al. Cell 144, 67-78 (2011). |
