TY - JOUR A2 - Avila, Jesús AU - Desforges, Nicole M. AU - Hebron, Michaeline L. AU - Algarzae, Norah K. AU - Lonskaya, Irina AU - Moussa, Charbel E.-H. PY - 2012 DA - 2012/08/05 TI - Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases SP - 345472 VL - 2012 AB - The role of inflammation in neurodegenerative diseases has been widely demonstrated. Intraneuronal protein accumulation may regulate microglial activity via the fractalkine (CX3CL1) signaling pathway that provides a mechanism through which neurons communicate with microglia. CX3CL1 levels fluctuate in different stages of neurodegenerative diseases and in various animal models, warranting further investigation of the mechanisms underlying microglial response to pathogenic proteins, including Tau, β-amyloid (Aβ), and α-synuclein. The temporal relationship between microglial activity and localization of pathogenic proteins (intra- versus extracellular) likely determines whether neuroinflammation mitigates or exacerbates disease progression. Evidence in transgenic models suggests a beneficial effect of microglial activity on clearance of proteins like Aβ and a detrimental effect on Tau modification, but the role of CX3CL1 signaling in α-synucleinopathies is less clear. Here we review the nature of fractalkine-mediated neuronmicroglia interaction, which has significant implications for the efficacy of anti-inflammatory treatments during different stages of neurodegenerative pathology. Specifically, it is likely that anti-inflammatory treatment in early stages of disease during intraneuronal accumulation of proteins could be beneficial, while anti-inflammatory treatment in later stages when proteins are secreted to the extracellular space could exacerbate disease progression. SN - 2090-8024 UR - https://doi.org/10.1155/2012/345472 DO - 10.1155/2012/345472 JF - International Journal of Alzheimer’s Disease PB - Hindawi Publishing Corporation KW - ER -