Protein expression alteration in hippocampus upon genetic repression of AMPKα isoforms

Abstract

The AMP-activated protein kinase (AMPK) is a molecular sensor to help maintain cellular energy homeostasis. AMPK is a heterotrimeric complex and its enzymatic catalytic subunit includes two isoforms: α1 and α2. Dysregulation of AMPK signaling is linked to neuronal diseases characterized with cognitive impairments. Emerging evidence also suggest isoform-specific roles of AMPK in the brain. AMPK regulates protein synthesis, which is critical for memory formation and neuronal plasticity. However, the consequence of altering AMPK activity on the translation of specific proteins in the brain is unknown. Here, we use unbiased mass spectrometry-based proteomics approach to analyze protein profile alterations in hippocampus and prefrontal cortex of transgenic mice in which the genes for the two AMPKα isoforms are conditionally deleted. The study revealed identities of proteins whose expression is sensitive to suppression of AMPKα1 and/or α2 isoform. These data may serve as a basis for future in-depth study. Elucidation of the functional relevance of the alteration of specific proteins could provide insights into identification of novel therapeutic targets for neuronal disorders characterized with AMPK signaling dysregulation and impaired cellular energy metabolism.

Sorcin Activates the Brain PMCA and Blocks the Inhibitory Effects of Molecular Markers of Alzheimer’s Disease on the Pump Activity

“…Presenilins 1 and 2 have been found to form passive ER Ca 2+ leak channels, but this function is altered by mutations associated with familial AD, independently of its γ-secretase activities [ 21 ]. Recently, it has been shown that sorcin is downregulated in the hippocampus of mice with a partial repression of AMP-activated protein kinase, a protein that seems to be hyperactive in neurodegenerative disorders [ 22 ]. These studies point to a growing interest in sorcin research concentrated on the role it may play in neurodegeneration by regulating the function of other proteins involved in Ca 2+ signaling.…”