Role of Immune-Inflammatory Mechanisms in Alzheimer's Disease and Other Degenerative Diseases

ABSTRACT

Recent studies suggest that alterations of the immune-inflammatory system contribute to the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Neuroinflammatory response initiated by innate immune mechanism that self-attack on neurons, known as "autotoxicity" could be an initial key mechanism of chronic neurodegenerative diseases. Numerous experimental and pathological evidences showing upregulated inflammatory cytokines and chemokines, and the activation of complement cascade and accumulation of activated microglia in damaged regions support the important role of immune-inflammatory mechanism in the pathogenesis of neurodegenerative diseases. Epidemiological studies on the non-steroidal anti-inflammatory drugs (NSAIDs), coupled with results from animal model of AD, PD and ALS, have prompted the studies to determine if immune-inflammatory modifying agents or molecules could be a new therapeutic paradigm of neurodegenerative diseases. Molecules inhibiting proinflammatory cytokines and chemokines released from microglia, agents that inhibit activation of microglia, COX2 and complement system are now considered as a good candidate of immune-inflammatory modulating treatment. By better understanding inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approach that may not completely cure AD, PD, and ALS but will likely help slow the progression or delay the onset of these devastating diseases.