Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective
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 ne...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/1859431 |
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| author | Lucas Udovin Cecilia Quarracino María I. Herrera Francisco Capani Matilde Otero-Losada Santiago Perez-Lloret |
| author_facet | Lucas Udovin Cecilia Quarracino María I. Herrera Francisco Capani Matilde Otero-Losada Santiago Perez-Lloret |
| author_sort | Lucas Udovin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d372a0f3d28a4d9f86cf33fda100b4cc |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
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| series | Neural Plasticity |
| spelling | doaj-art-d372a0f3d28a4d9f86cf33fda100b4cc2025-02-03T05:49:55ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/18594311859431Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling PerspectiveLucas Udovin0Cecilia Quarracino1María I. Herrera2Francisco Capani3Matilde Otero-Losada4Santiago Perez-Lloret5Institute of Cardiological Research, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Marcelo T. de Alvear 2270, C1122 Buenos Aires, ArgentinaInstitute of Cardiological Research, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Marcelo T. de Alvear 2270, C1122 Buenos Aires, ArgentinaInstitute of Cardiological Research, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Marcelo T. de Alvear 2270, C1122 Buenos Aires, ArgentinaPontifical Catholic University of Argentina, Buenos Aires, ArgentinaInstitute of Cardiological Research, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Marcelo T. de Alvear 2270, C1122 Buenos Aires, ArgentinaInstitute of Cardiological Research, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Marcelo T. de Alvear 2270, C1122 Buenos Aires, ArgentinaDespite 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.http://dx.doi.org/10.1155/2020/1859431 |
| spellingShingle | Lucas Udovin Cecilia Quarracino María I. Herrera Francisco Capani Matilde Otero-Losada Santiago Perez-Lloret Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective Neural Plasticity |
| title | Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective |
| title_full | Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective |
| title_fullStr | Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective |
| title_full_unstemmed | Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective |
| title_short | Role of Astrocytic Dysfunction in the Pathogenesis of Parkinson’s Disease Animal Models from a Molecular Signaling Perspective |
| title_sort | role of astrocytic dysfunction in the pathogenesis of parkinson s disease animal models from a molecular signaling perspective |
| url | http://dx.doi.org/10.1155/2020/1859431 |
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