The role of extracellular alpha synuclein in molecular mechanisms of cell death

Abstract

Recently published data demonstrated that increased release, oligomerization and toxicity of α-synuclein (ASN) is a key molecular process in pathophysiology of neurodegenerative diseases classified as synucleinopathies (e.g. Parkinson disease or Alzheimer's disease). It was proved that the excessive release of ASN into the extracellular space, driven by environmental factors as well as neurodegeneration, may have a significant role in the spread of the neurodegeneration process within the brain. Extracellular ASN was shown to be toxic both to neurons and glial cells and the mechanism of its action depends on the concentration of this protein in the extracellular space. Exogenous ASN leads to the activation of plasma membrane receptors, causes increased calcium influx, and stimulates the synthesis of proinflammatory cytokines and nitric oxide, which in turn leads to activation of programmed cell death. These data provide new insights into the involvement of ASN in the neurodegenerative diseases, and thus can serve effectively for the development of their new therapy.