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Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders

Translational Neurodegeneration 2014年第1期3卷 180-203,179页

作者： Kristi M Anderson Katherine E Olson Katherine A Estes ken flanagan Howard E Gendelman R Lee Mosley Department of Pharmacology and Experimental Neuroscience Center for Neurodegenerative DisordersThe University of Nebraska Medical CenterOmahaNE 68198USA Prothena Biosciences Inc.650 Gateway BoulevardSouth San FranciscoCA 94080USA

Inappropriate T cell responses in the central nervous system(CNS)affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include,but are not limited to,multiple sclerosis,amyotrophic lateral sclerosis,Alzheimer’s disease and Parkinson’s *** the one hand immune responses can exacerbate neurotoxic responses;while on the other hand,they can lead to neuroprotective *** temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent ***,immune responses that affect neurodegeneration may occur within or outside the *** of antigen-specific CD4+T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal *** destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T ***,immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the *** responses with predominate T cell subtypes may differentially manifest migratory,regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific *** final result is altered glial and neuronal behaviors that influence the disease ***,discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.

关键词： Neurodegeneration Neuroprotection Migration MPTP MCAM Regulatory T cell Effector T cell,Neuroinflammation

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