[olsen]

Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7217-22. Epub 2007 Apr
16. Links
Resveratrol stimulates AMP kinase activity in neurons.

Dasgupta B, Milbrandt J.
Departments of Pathology, Washington University School of Medicine,
660 South Euclid Avenue, St. Louis, MO 63110, USA.

Resveratrol is a polyphenol produced by plants that has multiple
beneficial activities similar to those associated with caloric
restriction (CR), such as increased life span and delay in the onset
of diseases associated with aging. CR improves neuronal health, and
the global beneficial effects of CR have been postulated to be
mediated by the nervous system. One key enzyme thought to be activated
during CR is the AMP-activated kinase (AMPK), a sensor of cellular
energy levels. AMPK is activated by increases in the cellular AMP:ATP
ratio, whereupon it functions to help preserve cellular energy. In
this regard, the regulation of dietary food intake by hypothalamic
neurons is mediated by AMPK. The suppression of nonessential energy
expenditure by activated AMPK along with the CR mimetic and
neuroprotective properties of resveratrol led us to hypothesize that
neuronal activation of AMPK could be an important component of
resveratrol activity. Here, we show that resveratrol activated AMPK in
Neuro2a cells and primary neurons in vitro as well as in the brain.
Resveratrol and the AMPK-activating compound 5-aminoimidazole-4-
carboxamide-1-beta-D-ribofuranoside (AICAR) promoted robust neurite
outgrowth in Neuro2a cells, which was blocked by genetic and
pharmacologic inhibition of AMPK. Resveratrol also stimulated
mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-
stimulated AMPK activity in neurons depended on LKB1 activity but did
not require the NAD-dependent protein deacetylase SIRT1 during this
time frame. These findings suggest that neuronal activation of AMPK by
resveratrol could affect neuronal energy homeostasis and contribute to
the neuroprotective effects of resveratrol.


PMID: 17438283 [PubMed - indexed for MEDLINE]


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