アンモニアが関与する脳内老化システム

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  • Induction of astrocyte senescence by ammonia.

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<p>Alz­heimer’s dis­ease (AD) is the most common neuro­degenerative dis­ease characterized by cognitive decline and irreversible memory loss. Excessive amount of ammonia has been detected in the brain and serum of AD patients, and the toxicity of ammonia has been thought as a factor which con­tri­butes to the pro­gression of AD. In the central nervous system, astro­cytes play a key role in ammonia meta­bolism by ex­pressing the enzyme called glutamine synthetase, which catalyzes the synthesis of glutamine from glu­tam­ate and ammonia, and supply glutamine to neu­rons for the pro­duction of neuro­trans­mitters. Here we report that pro­longed NH4Cl treat­ment accumulates amyloid pre­cursor pro­tein (APP) in astro­cytes. Enhanced APP levels was detected in both the plasma mem­branes and in­tra­cellular com­partments. Immuno­cyto­chemistry revealed that NH4Cl induces the accu­mulation of APP in the endo­plasmic reticulum and cleaved to become amyloid beta. In addition, NH4Cl treat­ment induced astrocyte senescence, which inhibits cell proliferation. To­gether, our data sug­gests that ammonia induces the pro­duction and accu­mulation of APP and Aβ in astro­cytes as well as astrocyte senescence, and possibly exacerbate AD patho­logy.</p>

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