Astrocytes and Therapeutics for Parkinson's Disease
Identifieur interne : 000167 ( Pmc/Curation ); précédent : 000166; suivant : 000168Astrocytes and Therapeutics for Parkinson's Disease
Auteurs : Phillip Rappold ; Kim TieuSource :
- Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [ 1933-7213 ] ; 2010.
Abstract
Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in Amyotrophic Lateral Sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context dependent dual role of astrocytes has also been documented in experimental models of Parkinson's disease (PD). These studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in PD will be discussed in this review. More specifically, we will examine how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release pro-inflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of PD constitute an exciting development with promising novel therapeutic targets.
Url:
DOI: 10.1016/j.nurt.2010.07.001
PubMed: 20880505
PubMed Central: 2948546
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<series><title level="j">Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics</title>
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<front><div type="abstract" xml:lang="en"><p id="P1">Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in Amyotrophic Lateral Sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context dependent dual role of astrocytes has also been documented in experimental models of Parkinson's disease (PD). These studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in PD will be discussed in this review. More specifically, we will examine how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release pro-inflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of PD constitute an exciting development with promising novel therapeutic targets.</p>
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<journal-title>Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics</journal-title>
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<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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<title-group><article-title>Astrocytes and Therapeutics for Parkinson's Disease</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Rappold</surname>
<given-names>Phillip M.</given-names>
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<contrib contrib-type="author"><name><surname>Tieu</surname>
<given-names>Kim</given-names>
</name>
<xref rid="FN1" ref-type="author-notes">*</xref>
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<aff id="A1">Department of Neurology in the Center for Translational Neuromedicine, University of Rochester School of Medicine and Dentistry, New York, 14642</aff>
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<author-notes><corresp id="FN1"><label>*</label>
To whom correspondence to be addressed: Department of Neurology in the Center for Translational Neuromedicine, University of Rochester School of Medicine, 575 Elmwood Avenue, Box 645, Rochester, NY, 14642, Tel: 585-273-4681, Fax: 585-276-2298, <email>kim_tieu@urmc.rochester.edu</email>
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<pub-date pub-type="nihms-submitted"><day>23</day>
<month>7</month>
<year>2010</year>
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<pub-date pub-type="ppub"><month>10</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>10</month>
<year>2011</year>
</pub-date>
<volume>7</volume>
<issue>4</issue>
<fpage>413</fpage>
<lpage>423</lpage>
<abstract><p id="P1">Astrocytes play direct, active, and critical roles in mediating neuronal survival and function in various neurodegenerative disorders. This role of astrocytes is well illustrated in Amyotrophic Lateral Sclerosis (ALS), in which the removal of glutamate from the extracellular space by astrocytes confers neuroprotection, whereas astrocytic release of soluble toxic molecules promotes neurodegeneration. In recent years, this context dependent dual role of astrocytes has also been documented in experimental models of Parkinson's disease (PD). These studies and some potential mechanisms by which astrocytes may influence the neurodegenerative processes in PD will be discussed in this review. More specifically, we will examine how astrocytes confer neuroprotection either through the removal of toxic molecules from the extracellular space or through the release of trophic factors and antioxidant molecules. In contrast, under pathological conditions, astrocytes release pro-inflammatory cytokines and other toxic molecules that are detrimental to dopaminergic neurons. These emerging roles of astrocytes in the pathogenesis of PD constitute an exciting development with promising novel therapeutic targets.</p>
</abstract>
<kwd-group><kwd>Parkinson's disease</kwd>
<kwd>astrocytes</kwd>
<kwd>neurodegeneration</kwd>
<kwd>dopamine</kwd>
<kwd>glial-neuronal interactions</kwd>
<kwd>neurodegenerative diseases</kwd>
</kwd-group>
<contract-num rid="ES1">R21 ES017470-01
||ES</contract-num>
<contract-num rid="ES1">R01 ES014899-04
||ES</contract-num>
<contract-sponsor id="ES1">National Institute of Environmental Health Sciences : NIEHS</contract-sponsor>
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