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Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder?
Int Rev Neurobiol. 2007; 82:235-46.IR

Abstract

Microglial activation similar to that which occurs in peripheral macrophages during inflammatory attack was first demonstrated in the Alzheimer's disease (AD) brain two decades ago. Localization to pathologically vulnerable regions of AD cortex, localization to sites of specific AD pathology such as amyloid-beta peptide (Abeta) deposits, and the ability of activated microglia to release toxic inflammatory factors suggested that the activation of microglia in AD might play a pathogenic role. However, proving this hypothesis in a disease in which so many profound pathologies occur (e.g., Abeta deposition, neurofibrillary tangle formation, inflammation, neuronal loss, neuritic loss, synaptic loss, neuronal dysfunction, vascular alterations) has proven difficult. Although investigations of microglia in Parkinson's disease (PD) are more recent and therefore less extensive, demonstration of a pathogenic role for microglial activation may actually be much simpler in PD than AD because the root pathological event in PD, loss of dopamine (DA)-secreting substantia nigra neurons, is already well established. Indeed, indirect but converging evidence of a pathogenic role for activated microglia in PD has already begun to emerge. The nigra reportedly has the highest density of microglia in brain, and, in PD, nigral microglia are not only highly activated but also highly clustered around dystrophic DA neurons. 6-OHDA and MPTP models of PD in rodents induce substantia nigra microglial activation. More cogent, injections of the classic microglial/macrophage activator lipopolysaccharide into or near the rodent nigra cause a specific loss of DA neurons there. Culture models with human microglia and human cellular targets replicate this phenomenon. Notably, nearly all the proposed etiologies of PD, including brain bacterial and viral exposure, pesticides, drug contaminants, and repeated head trauma, are known to cause brain inflammation. A mechanism by which activated microglia might specifically target DA neurons remains a critical missing link in the proof of a pathogenic role for activated microglia in PD. If such a link could be established, however, clinical intervention trials with agents that dampen microglial activation might be warranted in PD.

Authors+Show Affiliations

The L. J. Roberts Center for Alzheimer's Research, Sun Health Research Institute Sun City, Arizona 85351, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17678964

Citation

Rogers, Joseph, et al. "Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder?" International Review of Neurobiology, vol. 82, 2007, pp. 235-46.
Rogers J, Mastroeni D, Leonard B, et al. Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder? Int Rev Neurobiol. 2007;82:235-46.
Rogers, J., Mastroeni, D., Leonard, B., Joyce, J., & Grover, A. (2007). Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder? International Review of Neurobiology, 82, 235-46.
Rogers J, et al. Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder. Int Rev Neurobiol. 2007;82:235-46. PubMed PMID: 17678964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder? AU - Rogers,Joseph, AU - Mastroeni,Diego, AU - Leonard,Brian, AU - Joyce,Jeffrey, AU - Grover,Andrew, PY - 2007/8/7/pubmed PY - 2007/9/6/medline PY - 2007/8/7/entrez SP - 235 EP - 46 JF - International review of neurobiology JO - Int Rev Neurobiol VL - 82 N2 - Microglial activation similar to that which occurs in peripheral macrophages during inflammatory attack was first demonstrated in the Alzheimer's disease (AD) brain two decades ago. Localization to pathologically vulnerable regions of AD cortex, localization to sites of specific AD pathology such as amyloid-beta peptide (Abeta) deposits, and the ability of activated microglia to release toxic inflammatory factors suggested that the activation of microglia in AD might play a pathogenic role. However, proving this hypothesis in a disease in which so many profound pathologies occur (e.g., Abeta deposition, neurofibrillary tangle formation, inflammation, neuronal loss, neuritic loss, synaptic loss, neuronal dysfunction, vascular alterations) has proven difficult. Although investigations of microglia in Parkinson's disease (PD) are more recent and therefore less extensive, demonstration of a pathogenic role for microglial activation may actually be much simpler in PD than AD because the root pathological event in PD, loss of dopamine (DA)-secreting substantia nigra neurons, is already well established. Indeed, indirect but converging evidence of a pathogenic role for activated microglia in PD has already begun to emerge. The nigra reportedly has the highest density of microglia in brain, and, in PD, nigral microglia are not only highly activated but also highly clustered around dystrophic DA neurons. 6-OHDA and MPTP models of PD in rodents induce substantia nigra microglial activation. More cogent, injections of the classic microglial/macrophage activator lipopolysaccharide into or near the rodent nigra cause a specific loss of DA neurons there. Culture models with human microglia and human cellular targets replicate this phenomenon. Notably, nearly all the proposed etiologies of PD, including brain bacterial and viral exposure, pesticides, drug contaminants, and repeated head trauma, are known to cause brain inflammation. A mechanism by which activated microglia might specifically target DA neurons remains a critical missing link in the proof of a pathogenic role for activated microglia in PD. If such a link could be established, however, clinical intervention trials with agents that dampen microglial activation might be warranted in PD. SN - 0074-7742 UR - https://www.unboundmedicine.com/medline/citation/17678964/Neuroinflammation_in_Alzheimer's_disease_and_Parkinson's_disease:_are_microglia_pathogenic_in_either_disorder L2 - https://linkinghub.elsevier.com/retrieve/pii/S0074-7742(07)82012-5 DB - PRIME DP - Unbound Medicine ER -