Exosomes: a novel therapeutic target for Alzheimer's disease?

Abstract

Extracellular exosomes are formed inside the cytoplasm of cells in compartments known as multivesicular bodies. Thus, exosomes contain cytoplasmic content. Multivesicular bodies fuse with the plasma membrane and release exosomes into the extracellular environment. Comprehensive research suggests that exosomes act as both inflammatory intermediaries and critical inducers of oxidative stress to drive progression of Alzheimer's disease. An important role of exosomes in Alzheimer's disease includes the formation of neurofibrillary tangles and beta-amyloid production, clearance, and accumulation. In addition, exosomes are involved in neuroinflammation and oxidative stress, which both act as triggers for beta-amyloid pathogenesis and tau hyperphosphorylation. Further, it has been shown that exosomes are strongly associated with beta-amyloid clearance. Thus, effective measures for regulating exosome metabolism may be novel drug targets for Alzheimer's disease.

Keywords: beta-amyloid; dementia; microvesicle; nerve regeneration; neural regeneration; neurodegeneration; neuroinflammation; oxidative stress; tau; therapeutic target.

Figure 1

Schematic diagram of the emerging role of exosomes in beta-amyloid peptide pathology. Exosomes are formed inside multivesicular bodies in cells. Exosomes are released into the extracellular environment when multivesicular bodies fuse with the plasma membrane. Beta-amyloid (Aβ) can be secreted from cells by association with exosomes. Aβ secreted from exosomes in the extracellular space contributes to Aβ plaque formation, which in turn triggers neuroinflammation and oxidative stress.