Protein expression alteration in hippocampus upon genetic repression of AMPKα isoforms

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: alpha 1 and alpha 2. 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 AMPK alpha isoforms are conditionally deleted. The study revealed identities of proteins whose expression is sensitive to suppression of AMPK alpha 1 and/or alpha 2 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.

Automated summary

AMP-activated protein kinase (AMPK) plays a crucial role in maintaining cellular energy balance and dysregulation of its signaling is linked to neuronal diseases. This study identified proteins sensitive to suppression of AMPK alpha isoforms, potentially informing future research on therapeutic targets for neurological disorders.