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Glial reactions in Parkinson's disease.
Mov Disord. 2008 Mar 15; 23(4):474-83.MD

Abstract

Dopaminergic neurons of the substantia nigra are particularly vulnerable to oxidative and inflammatory attack. Such processes may play a crucial role in the etiology of Parkinson disease (PD). Since glia are the main generators of these processes, the possibility that PD may be caused by glial dysfunction needs to be considered. This review concentrates on glial reactions in PD. Reactive astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD cases indicating a robust inflammatory state. Glia normally serve neuroprotective roles but, given adverse stimulation, they may contribute to damaging chronic inflammation. Microglia, the phagocytes of brain, may be the main contributors since they can produce large numbers of superoxide anions and other neurotoxins. Their toxicity towards dopaminergic neurons has been demonstrated in tissue culture and various animal models of PD. The MPTP and alpha-synuclein models are of particular interest. Years after exposure to MPTP, inflammation has been observed in the SN. This has established that an acute insult to the SN can result in a sustained local inflammation. The alpha-synuclein model indicates that an endogenous protein can induce inflammation, and, when overexpressed, can lead to autosomal dominant PD. Less is known about the role of astrocytes than microglia, but they are known to secrete both inflammatory and anti-inflammatory molecules and may play a role in modulating microglial activity. Oligodendrocytes do not seem to play a role in promoting inflammation although, like neurons, they may be damaged by inflammatory processes. Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches.

Authors+Show Affiliations

Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada. mcgeerpl@interchange.ubc.caNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18044695

Citation

McGeer, Patrick L., and Edith G. McGeer. "Glial Reactions in Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 23, no. 4, 2008, pp. 474-83.
McGeer PL, McGeer EG. Glial reactions in Parkinson's disease. Mov Disord. 2008;23(4):474-83.
McGeer, P. L., & McGeer, E. G. (2008). Glial reactions in Parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 23(4), 474-83.
McGeer PL, McGeer EG. Glial Reactions in Parkinson's Disease. Mov Disord. 2008 Mar 15;23(4):474-83. PubMed PMID: 18044695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glial reactions in Parkinson's disease. AU - McGeer,Patrick L, AU - McGeer,Edith G, PY - 2007/11/30/pubmed PY - 2008/7/23/medline PY - 2007/11/30/entrez SP - 474 EP - 83 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 23 IS - 4 N2 - Dopaminergic neurons of the substantia nigra are particularly vulnerable to oxidative and inflammatory attack. Such processes may play a crucial role in the etiology of Parkinson disease (PD). Since glia are the main generators of these processes, the possibility that PD may be caused by glial dysfunction needs to be considered. This review concentrates on glial reactions in PD. Reactive astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD cases indicating a robust inflammatory state. Glia normally serve neuroprotective roles but, given adverse stimulation, they may contribute to damaging chronic inflammation. Microglia, the phagocytes of brain, may be the main contributors since they can produce large numbers of superoxide anions and other neurotoxins. Their toxicity towards dopaminergic neurons has been demonstrated in tissue culture and various animal models of PD. The MPTP and alpha-synuclein models are of particular interest. Years after exposure to MPTP, inflammation has been observed in the SN. This has established that an acute insult to the SN can result in a sustained local inflammation. The alpha-synuclein model indicates that an endogenous protein can induce inflammation, and, when overexpressed, can lead to autosomal dominant PD. Less is known about the role of astrocytes than microglia, but they are known to secrete both inflammatory and anti-inflammatory molecules and may play a role in modulating microglial activity. Oligodendrocytes do not seem to play a role in promoting inflammation although, like neurons, they may be damaged by inflammatory processes. Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/18044695/Glial_reactions_in_Parkinson's_disease_ L2 - https://doi.org/10.1002/mds.21751 DB - PRIME DP - Unbound Medicine ER -