Exosomes-associated neurodegeneration and progression of Parkinson's disease

Abstract

Growing evidence indicates the role of exosomes in a variety of physiological pathways as conveyors of biological materials from cell-to-cell. However the molecular mechanism(s) of secretion and their interaction with receiving cells are yet unclear. Recently, it is emerging that exosomes are involved in pathological processes as potential carriers in the progression of neurodegenerative pathologies associated with misfolded proteins. In the current review we will discuss some recent findings on the key role of exosomes in the spreading of the aggregated products of α-synuclein from neuron-to-neuron and of inflammatory response propagation from immune cell-to-cell; we will highlight the implication of exosomes in the neurodegeneration and progression of the disease and the their potential interplay with genes related to Parkinson's disease. Increasing our knowledge on the cell-to-cell transmissions might provide new insights into mechanism of disease onset and progression and identify novel strategies for diagnosis and therapeutic intervention in Parkinson and other neurodegenerative diseases.

Keywords: Exosomes; LRRK2; Parkinson’s disease; neuronal degeneration; α-synuclein.

Figure 1

Exosomes in the cell-to-cell communications and their role in the progression of PD. Exosomes containing α-Syn released by injured neurons can be transmitted from neuron-to-neuron thus leading to α-Syn spreading, and from neuron-to-glia leading to activation of inflammatory response. In turn, exosomes released by activated glial cells, containing inflammatory mediators, can be transmitted from glia-to-glia leading to the propagation of inflammatory response. Consecutively, the propagation of inflammatory mediators and the exacerbated neuroinflammation could contribute to neuronal dysfunctions and to progression of the disease.