| 摘要 |
Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment, and compromised integrity of neuronal dendrites. The role of Protein Kinase C(PKC) in age-related prefrontal cortical impairments had not been previously determined. The inventors provides evidence that PKC activity is associated with prefrontal cortical dysfunction in aging. The inventors provide methods of reversing the effects of prefrontal cortical decline, improving cognition, and improving working memory in aged subjects by providing a phenanthridinium alkaloid or closely related compound to the subject. The inventors found chelerythrine reversed working memory impairments in aged rats and enhanced working memory in aged rhesus monkeys. Improvement correlated with age, with older monkeys demonstrating a greater degree of improvement following PKC inhibition. The inventors findings indicate that PKC is dysregulated in aged subjects and that PKC inhibitors may be used to treatment improve cognition in the elderly.
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