Cell Responses to Extracellular α-Synuclein

Abstract

Synucleins are small naturally unfolded proteins involved in neurodegenerative diseases and cancer. The family contains three members: α-, β-, and -synuclein. α-Synuclein is the most thoroughly investigated because of its close association with Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Until recently, the synuclein's research was mainly focused on their intracellular forms. However, new studies highlighted the important role of extracellular synucleins. Extracellular forms of synucleins propagate between various types of cells, bind to cell surface receptors and transmit signals, regulating numerous intracellular processes. Here we give an update of the latest results about the mechanisms of action of extracellular synucleins, their binding to cell surface receptors, effect on biochemical pathways and the role in neurodegeneration and neuroinflammation.

Keywords: Parkinson's disease; conformational diseases; glaucoma; integrins; matrix metalloproteinases; neurodegeneration; protein misfolding; synucleins.

Figure 1

The effect of extracellular α-synuclein binding to cellular receptor on neuronal or glial cells. Various proteins may fulfill the role of such receptors, including PrPC, LAG3, neurexin 1α [17], TLR2 [23], mGluR5 [12], Fc gamma receptor IIb [24] (Table 1) and others. Gangliosides in the lipid rafts can also act as receptors for extracellular α-synuclein [25]. A–a cell in the absence of extracellular α-synuclein, B–cellular response on α-synuclein binding.