Therapeutic functions of astrocytes to treat α-synuclein pathology in Parkinson’s disease

Abstract

Parkinson's disease (PD) is an age-related neurodegenerative disease that accompanies motor symptoms, characterized by loss of dopaminergic (DA) neurotransmission in substantia nigra pars compacta of the midbrain. Also, a pathologic hallmark of PD is intra-neuronal the accumulation of alpha-synuclein (α-syn) aggregates, called Lewy body and Lewy neurites. The α-syn aggregate is suggested as an important key target in neurodegeneration in Parkinson's or other neurodegenerative diseases. While much research is being done on α-syn for the treatment of PD, no therapeutic intervention to effectively relieve α-synuclinopathy has been developed. In this study, I provide evidences that cultured astrocytes, especially those derived from ventral midbrain (VM) where mDA neurons are developed and reside, exerted therapeutic actions to reduce α-synucleinopathy in neuronal cells by regulating a series of procedures associated with formation and transmission of toxic α-syn aggregates. Based on these findings, I propose that astrocyte conditioned media could be a promising source for PD drug discovery and astrocyte could be a candidate supporting cell source for stem cell-based PD therapy which is free from the host-to-graft propagation of toxic α-syn.