Microglia as a Target for Inflammatory Processes and Neuroprotective Strategies
Abstract:The importance of glial cell-propagated inflammation (i.e., neuroinflammation) disorders such as Alzheimer's disease (AD) was viewed previously as a bystander effect, or epiphenomenon, with inflammation occurring when damaged neurons elicit an activation response by glia. A growing body of evidence is now challenging this earlier perspective and points to a more active role of neuroinflammation in the pathophysiology of progressive neurodegenerative disorders such as AD, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. This insight into pathophysiology evolved in concert with an appreciation of the brain not being as immunologically privileged as once thought. The central nervous system has its own resident immune system, in which glial cells (microglia, astrocytes, and oligodendrocytes) not only serve supportive and nutritive roles for neurons but also engage from time to time in several "inflammatory" processes that defend the central nervous system from pathogens and help it to recover from stress and injury. Indeed, recent in vivo studies have shown that microglia carry out active tissue scanning, which challenges the traditional notion of 'resting' microglia in the normal brain. These otherwise "normal" glial functions can sometimes result in a more severe and chronic neuroinflammatory cycle that actually promotes or propagates neurodegenerative disease. Excessive glial cell activation may thus constitute a viable target for the discovery and development of neurodegenerative disease-based therapeutics. Suggestive clinical evidence in support of neuroinflammation as a drug discovery target for chronic neurodegenerative diseases, such as AD, comes from epidemiological and genetic linkage data. For example, long-term use of non-steroidal anti-inflammatory drugs is correlated with a protective effect against AD, and certain polymorphisms in the genes for interleukin 1 and other pro-inflammatory mediator genes are associated with increased risk. In AD and Parkinson's disease, activated microglia and complement proteins have been identified in the brain regions most affected in these disorders. The focus of this review will be to assess clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation, and potential targets for pharmacological intervention.
Document Type: Review Article
Publication date: June 1, 2010
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- This journal aims to focus specifically on the emerging new aspects of neuroprotection and neuroregeneration in the widest sense of neuroscience. American Journal of Neuroprotection and Neuroregeneration (AJNN) deals with research on all the aspects of the central nervous system: relevant CNS diseases, their processes and their modification with drugs that may have any influence and significance in experimental and clinical conditions.
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