Brain Aging and Neuroinflammation

Recently, inflammation has been recognized as playing a central role in the cognitive decline too often associated with Aging. Inflammation is now thought to play a major role in pathological conditions ranging from cardiovascular diseases to Alzheimer disease, implicating it in many more diseases than was previously thought. Inflammation becomes particularly relevant in several neurological disorders, such as Alzheimer disease and vascular dementia. Although mental decline and memory loss have long been considered inevitable hallmarks of old age, new research suggests that such inflammation/age-associated decline is avoidable. Indeed, early intervention to limit damage associated with inflammation and free radicals may offer some protection against these dreaded brain diseases.

Low-grade chronic inflammation (as opposed to acute), generally unnoticed, is believed to underlie the most serious neurodegenerative diseases. Consequently, anti-inflammatory drugs, such as the non-steroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin, ibuprofen, and acetaminophen) and the newer COX-2 inhibitors (e.g., Celebrex and Vioxx), are being investigated. Another main objective of Dr. Doré’s research is to understand the actions of cyclooxygenase and its metabolites, the prostaglandins. The overall goal is to develop more selective action that would specifically relieve inflammation while minimizing the distressing side effects that are possible with chronic use of the currently available drugs (either over-the-counter or prescribed).

Selected References:

  1. Doré S et al., Neuronal overexpression of cyclooxygenases-2 increases cerebral infarction. Annals of Neurology 54:155 62, 2003.
  2. Doré S. Decreased activity of the anti-oxidant heme-oxygenase enzyme: implications in ischemia and in Alzheimer’s disease. Free Radical Res 32:1276-82, 2002.
  3. Doré S*, Law A*, Blackshaw S, Gauthier S, Quirion R. Alteration of expression levels of neuronal nitric oxide synthase and Heme Oxygenase-2 (HO2) messenger RNA in the hippocampi and cortices of young and aged-cognitively unimpaired and impaired Long-Evan’s rats. Neuroscience 100:769-75, 2000.
  4. Doré S, Kar S, Quirion R. Insulin-like growth factor-I protects and rescues hippocampal neurons against ß-amyloid and human amylin toxicity. Proc Natl Acad Sci U S A 94:4772-7, 1997.

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