Artículos de revistas
Role of astrocytic dysfunction in the pathogenesis of parkinson’s disease animal models from a molecular signaling perspective
Fecha
2020Registro en:
2090-5904 (impreso)
1687-5443 (online)
10.1155/2020/1859431
Autor
Udovin, Lucas Daniel
Quarracino, Cecilia
Herrera, María Inés
Capani, Francisco
Otero Losada, Matilde
Pérez Lloret, Santiago
Institución
Resumen
Resumen: Despite the fact that astrocytes are the most abundant glial cells, critical for brain function, few studies have dealt with their possible
role in neurodegenerative diseases like Parkinson’s disease (PD). This article explores relevant evidence on the involvement of
astrocytes in experimental PD neurodegeneration from a molecular signaling perspective. For a long time, astrocytic
proliferation was merely considered a byproduct of neuroinflammation, but by the time being, it is clear that astrocytic
dysfunction plays a far more important role in PD pathophysiology. Indeed, ongoing experimental evidence suggests the
importance of astrocytes and dopaminergic neurons’ cross-linking signaling pathways. The Wnt-1 (wingless-type MMTV
integration site family, member 1) pathway regulates several processes including neuron survival, synapse plasticity, and
neurogenesis. In PD animal models, Frizzled (Fzd) neuronal receptors’ activation by the Wnt-1 normally released by astrocytes
following injuries leads to β-catenin-dependent gene expression, favoring neuron survival and viability. The transient receptor
potential vanilloid 1 (TRPV1) capsaicin receptor also participates in experimental PD genesis. Activation of astrocyte TRPV1
receptors 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 potential
of normalizing astrocyte function in PD.