Several genes encode these subunits (α1, α2, β1, β2, γ1, γ2, γ3) giving rise to a multitude of complexes. AMPK is a hetero-trimeric complex composed of a catalytic α subunit and two regulatory β and γ subunits. In this context, AMPK acts by phosphorylating key enzymes in metabolic pathways as well as transcriptional factors and cofactors. These results show that AMPK regulates tau phosphorylation in mouse primary neurons as well as in vivo and thus suggest that AMPK could be a key player in the development of AD pathology.ĪMP-activated protein kinase (AMPK) is a master energy sensor whose activation following energy stress conditions helps maintain cellular energy levels. Finally, we found that AMPK deficiency reduced tau pathology in the PS19 mouse model of tauopathy. We further show that AMPK mice deficient for one of the catalytic alpha subunits displayed reduced endogenous tau phosphorylation. Here, we find that endogenous AMPK activation in mouse primary neurons induced an increase of tau phosphorylation at multiple sites, whereas AMPK inhibition led to a rapid decrease of tau phosphorylation. Besides, it was found that AMPK was a tau kinase in vitro. Recently, it has been demonstrated that AMP-activated protein kinase (AMPK) was deregulated in the brain of Alzheimer’s disease (AD) patients where it co-localized with phosphorylated tau in pre-tangle and tangle-bearing neurons. As a consequence, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status. NFTs result from the intracellular aggregation of abnormally and hyperphosphorylated tau proteins. Neurofibrillary tangles (NFTs) are the pathological hallmark of neurodegenerative diseases commonly known as tauopathies.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |