Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective

UDOVIN, LUCAS; QUARRACINO, CECILIA; HERRERA, MARÍA I.; CAPANI, FRANCISCO; OTERO-LOSADA, MATILDE; PEREZ-LLORET, SANTIAGO

Neural Plasticity

Hindawi Publishing Corporation

Año: 2020 vol. 2020 p. 1 - 10

2090-5904

Despite the fact that astrocytes are the most abundant glial cells, critical for brain function, few studies have dealt with their possiblerole in neurodegenerative diseases like Parkinson?s disease (PD). This article explores relevant evidence on the involvement ofastrocytes in experimental PD neurodegeneration from a molecular signaling perspective. For a long time, astrocyticproliferation was merely considered a byproduct of neuroinflammation, but by the time being, it is clear that astrocyticdysfunction plays a far more important role in PD pathophysiology. Indeed, ongoing experimental evidence suggests theimportance of astrocytes and dopaminergic neurons? cross-linking signaling pathways. The Wnt-1 (wingless-type MMTVintegration site family, member 1) pathway regulates several processes including neuron survival, synapse plasticity, andneurogenesis. In PD animal models, Frizzled (Fzd) neuronal receptors? activation by the Wnt-1 normally released by astrocytesfollowing injuries leads to β-catenin-dependent gene expression, favoring neuron survival and viability. The transient receptorpotential vanilloid 1 (TRPV1) capsaicin receptor also participates in experimental PD genesis. Activation of astrocyte TRPV1receptors by noxious stimuli results in reduced inflammatory response and increased ciliary neurotrophic factor (CNTF)synthesis, which enhances neuronal survival and differentiation. Another major pathway involves IκB kinase (IKK)downregulation by ARL6ip5 (ADP-ribosylation-like factor 6 interacting protein 5, encoded by the cell differentiation-associated,JWA, gene). Typically, IKK releases the proinflammatory NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)molecule from its inhibitor. Therefore, by downregulating NF-κB inhibitor, ARL6ip5 promotes an anti-inflammatory response.The evidence provided by neurotoxin-induced PD animal models guarantees further research on the neuroprotective potentialof normalizing astrocyte function in PD