The Inflammatory Component of Neurodegenerative Diseases

FERRARI CC, PITOSSI FJ

Handbook of Neurochemistry and Molecular Neurobiology

Springer

Lugar: New York; Año: 2007; p. 395 - 406

Inflammation is a key component in the immunological defense of the organism against health-threatening pathogens. On the other hand, a dysregulated inflammatory response can lead to tissue damage and disease. In the central nervous system (CNS), the inflammatory response obeys different rules than the periphery. The presence of a selective blood–brain barrier, the lack of dendritic cells, the chronic downregulation of costimulatory molecules, and a bias towards an immunosuppressive environment are mainly responsible for the characteristic features of the inflammatory response in the CNS. Until recently, with the exception of multiple sclerosis, the inflammatory component present in major chronic neurodegenerative diseases has been regarded as a logical consequence of cell death with no major functional relevance but to remove cellular debris. However, inflammation is now known to have toxic and protective effects in chronic neurodegenerative diseases such as Parkinson´s, Alzheimer´s, and prion diseases. Microglial activation appears as a common feature to all these pathologies. However, microglial cells do not seem to be activated to an end-stage, proinflammatory phenotype during chronic neurodegeneration. Instead, they appear to be in a “primed” state where major proinflammatory cytokine production is tightly controlled. These observations are in agreement with the noninflammatory nature of apoptotic cell death. In addition, evidence is accumulating to favour the hypothesis that these “primed” microglial cells will produce an exacerbated amount of proinflammatory cytokines if a proinflammatory stimulus hits them in this state. The resulting exacerbated inflammatory response can lead to a toxic effect on the degenerating cells, exacerbating disease and aggravating symptoms. These observations are seminal to understand the pathophysiology of neurodegenerative diseases and prevent putative disease exacerbation by inflammation.