Microglia, Calcification and Neurodegenerative Diseases

1.1 Neurodegeneration involve different cell types Neurodegeneration is a complex process involving different cell types and neurotransmitters. A common characteristic of neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis, Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS) is the occurrence of a neuroinflammatory reaction in which cellular processes involving glial cells (mainly microglia and astrocytes) and T cells are activated in response to neuronal death. This inflammatory reaction has recently received attention as an unexpected potential target for the treatment of these diseases. Microglial cells have a mesenchymal origin, invade the central nervous system (CNS) prenatally (Chan et al., 2007b) and are the resident macrophages in the CNS (Ransohoff & Perry, 2009). They comprise approximately 10-20% of adult glia and serve as the CNS innate immune system. In neurodegenerative diseases, microglia is activated by misfolded proteins. In the case of AD, amyloid-┚ (A┚) peptides accumulate extracellularly and activate the microglia locally. In the case of PD, ALS and HD, the misfolded proteins accumulate intracellularly but are still associated with activation of the microglia (Perry et al., 2010). Reactive microglia in the substantia nigra and striatum of PD brains have been described, and increased levels of proinflammatory cytokines and inducible nitric oxide synthase have been detected in these brain regions, providing evidence of a local inflammatory reaction (Hirsch & Hunot, 2009). The injection of lipopolysaccharide (a potent microglia activator) into the substantia nigra produces microglial activation and the death of dopaminergic cells. These findings support the hypothesis that microglial activation and neuroinflammation contribute to PD pathogenesis (Herrera et al., 2000). Astrocytes are ectodermal cells, and they are probably about ten times as numerous as neurons. Astroglial cells were initially believed to be passive support cells providing trophic support for surrounding neurons (Sofroniew & Vinters, 2010), maintaining extracellular ion homeostasis and capturing excess extracellular neurotransmitters such as glutamate, which is considered particularly important given its involvement in excitotoxicity. However, recent studies have implicated astrocytes in many complex CNS functions, such as physical