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Trends Immunol. 2008 Aug;29(8):357-65. doi: 10.1016/ Epub 2008 Jul 1.

Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression.

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Neuropharmacology Section, Laboratory of Pharmacology, National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, NC 27709, USA.


Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in discrete areas of the central nervous system (CNS). The mechanism(s) underlying their progressive nature remains unknown but a timely and well-controlled inflammatory reaction is essential for the integrity and proper function of the CNS. Substantial evidence has documented a common inflammatory mechanism in various neurodegenerative diseases. We hypothesize that in the diseased CNS, interactions between damaged neurons and dysregulated, overactivated microglia create a vicious self-propagating cycle causing uncontrolled, prolonged inflammation that drives the chronic progression of neurodegenerative diseases. We further propose that dynamic modulation of this inflammatory reaction by interrupting the vicious cycle might become a disease-modifying therapeutic strategy for neurodegenerative diseases.

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