Cyclooxygenase and inflammation in Alzheimer's disease: Experimental approaches and clinical interventions

Abstract

Many epidemiological studies suggest that use of non-steroidal anti-inflammatory drugs (NSAIDs) delay or slow the clinical expression of Alzheimer's disease (AD). While it has been demonstrated that neurodegeneration in AD is accompanied by specific inflammatory mechanisms, including activation of the complement cascade and the accumulation and activation of microglia, the mechanism by which NSAIDs might affect these or other pathophysiological processes relevant to AD has been unclear. New evidence that cyclooxygenase (COX) is involved in neurodegeneration along with the development of selective COX inhibitors has led to renewed interest in the therapeutic potential of NSAIDs in AD.

Cyclooxygenase-2 Immunoreactivity and Protein Level in the Gerbil Hippocampus During Normal Aging

“…COX-2 participates in activity-dependent synapse formation, remodeling and post-synaptic signaling [7,19]. In addition, COX-2 is involved in mechanisms of neuronal death and survival [20].…”

Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

“…Cyclooxygenase (COX) converts membranederived arachidonic acid to prostaglandins, and generates free radicals: COX-2 is of primary importance in the inflammatory response (Pasinetti 1998;Lee et al 2008). It has been reported that systemic LPS treatment reduces brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the hippocampus (Guan and Fang 2006;Schnydrig et al 2007).…”

JNK inhibitor protects dopaminergic neurons by reducing COX-2 expression in the MPTP mouse model of subacute Parkinson's disease

“…COX-1 is expressed constitutively in many cell types, whereas COX-2 expression is generally induced by cytokines and other stress-induced stimuli [21]. In brain, COX-2 is present in selected neurons and its expression is upregulated in numerous pathological conditions, including Alzheimer's disease [22]. In addition, consistent with the inflammation hypothesis, epidemiological analysis has indicated that nonsteroid anti-inflammatory drugs (NSAIDs) may prevent or delay the progress of PD.…”

“…These NSAIDs are believed to target cyclooxygenase (COX), of which there are two isoforms, COX-1 and COX-2 [23]. Therefore, it is now believed that COX-2 is of primary importance in the inflammatory response [3,8,11,22,24]. JNKs (c-Jun N-terminal kinases) are a subfamily of mitogen-activated protein kinases.…”