Inflammation correlates with neurodegeneration but until recently, the association has been assumed to be a consequence of neurodegeneration and not a causal factor. A recent study supports the hypothesis that inflammation is at least a rate-limiting factor of neurodegeneration and may be a principal underlying cause in many cases. This signals a potential role for anti-inflammatory drugs in the treatment of dementia and other neurodegenerative diseases.
The study, published in Human Molecular Genetics, used human studies and animal models to find evidence supporting the hypothesis that inflammation proceeds neurodegeneration. It appears that genes associated with dementia play a role in regulating cellular inflammation. As we age, we accumulate mutations in our cells that can lead to our immune system categorizing cells with mutations as “non-self”, which in turn initiates an inflammatory response similar to the body’s response to a pathogen and ultimately causing, or at least contributing to, neurodegeneration.
This is not the first time researchers have suggested targeting inflammation mediators to treat dementia. An earlier study of anti-inflammatory drugs used to treat Alzheimer’s Disease argued for mitigating the effects of Alzheimer’s by using anti-inflammatory drugs to mediate the inflammatory response of microglia cells, a type of immune system cell found in the brain. This approach is supported by other studies that have found evidence from in vitro studies indicating that non-steroidal anti-inflammatory drugs (NSAID) can reduce the inflammatory response of microglia cells. Parkinson’s Disease is another neurodegenerative disease that may benefit from anti-inflammatory treatments. Glucocorticoids have been used to reduce brain inflammation and seem to modulate immune responses in multiple ways making them of interest to Parkinson’s Disease researchers.
It is important to note that not all immune responses associated with neurodegeneration follow the same pattern. Inflammatory microglia are often associated with senile plaques in Alzheimer’s Disease but the common inflammatory response is not. If anti-inflammatory drugs are to be used to treat Alzheimer’s Disease and other neuorodegenerative diseases, the drugs would need to be targeted to molecular mechanisms mediating the particular immune system process.
Further support for the use of anti-inflammatories for chronic disease treatment come from research into other multifactorial diseases. Inflammation’s role in multifactorial diseases such as rheumatoid arthritis, atherosclerosis, as well as metabolic syndrome and type 2 diabetes is well-established. For example, endothelial dysfunction occurs early in the onset of atherosclerosis. Increased levels of adhesion molecules and pro-inflammatory cytokines damage endothelial cells resulting in the progression of atherosclerosis. Studies in other diseases in which inflammation is implicated may help reveal additional insights into the molecular mechanisms of inflammatory responses.
The mediators of inflammation appear to have roles in a variety of chronic diseases. There are a variety types of inflammation mediators, from microRNAs to cytokines secreted from adipose tissue. Research into different mediators and their molecular function may help identify potential targets for anti-inflammatory drugs.
From here, the next step is to test existing anti-inflammatory drugs for effectiveness in reducing the effects of neurodegeneration and other chronic, multifactorial diseases.