Editors' ChoiceNeurobiology

Amyloid β-Peptide May Inhibit Cognitive Function

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Science's STKE  08 Oct 2002:
Vol. 2002, Issue 153, pp. tw363-TW363
DOI: 10.1126/stke.2002.153.tw363

Amyloid β-peptide (Aβ) is implicated in the progression of Alzheimer's disease, which is a neurodegenerative disease characterized by loss of cognitive function and neuron death. Vitolo et al. report that application of sublethal doses of Aβ applied to cultured hippocampal neurons inhibited protein kinase A (PKA) activity and reduced glutamate-stimulated phosphorylation of the PKA target CREB, a transcription factor involved in changes in gene expression associated with synaptic plasticity. In hippocampal slices, Aβ inhibited the induction of long-term potentiation. The effects of Aβ were reversed by coapplication of drugs that increase adenosine 3′,5′ -monophosphate (cAMP) concentrations. Thus, the cAMP-PKA pathway may be a potential target for therapeutic intervention in early stages of Alzheimer's disease caused by accumulation or release of Aβ.

O. V. Vitolo, A. Sant'Angelo, V. Constanzo, F. Battaglia, O. Arancio, M. Shelanski, Amyloid β-peptide inhibition of the pKA/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling. Proc. Natl. Acad. Sci. U.S.A. 99, 13217-13221 (2002). [Abstract] [Full Text]

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