Literature summary for 2.7.11.26 extracted from

Domise, M.; Didier, S.; Marinangeli, C.; Zhao, H.; Chandakkar, P.; Buee, L.; Viollet, B.; Davies, P.; Marambaud, P.; Vingtdeux, V.
AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo (2016), Sci. Rep., 6, 26758.

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Activating Compound

Activating Compound	Comment	Organism	Structure
AICAR	-	Mus musculus
AMP	AMP-activated protein kinase	Mus musculus
metformin	-	Mus musculus

Inhibitors

Inhibitors	Comment	Organism	Structure
compound C	inhibits tau protein phosphorylation by AMPK	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
microtubule	-	Mus musculus	5874	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + [tau-protein]	Mus musculus	AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons	ADP + O-phospho-[tau-protein]	-	?
ATP + [tau-protein]	Mus musculus C57BL6	AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons	ADP + O-phospho-[tau-protein]	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	Q5EG47	-	-
Mus musculus C57BL6	Q5EG47	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	the brain AMPK is mainly expressed in neurons	Mus musculus	-
neuron	primary neuronal cultures at 15 DIV	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + [tau-protein]	AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons	Mus musculus	ADP + O-phospho-[tau-protein]	-	?
ATP + [tau-protein]	AMPK phosphorylate tau in vitro at several epitopes including Thr231, Ser262/356, Ser396, Ser409 and Ser422, whereas Ser199, Ser202, Ser235, Ser400, and Ser404 are not phosphorylated by AMPK	Mus musculus	ADP + O-phospho-[tau-protein]	-	?
ATP + [tau-protein]	AMPK is one of the main tau kinase phosphorylating tau at the epitopes Ser262/356 and Thr231 at basal conditions in neurons	Mus musculus C57BL6	ADP + O-phospho-[tau-protein]	-	?
ATP + [tau-protein]	AMPK phosphorylate tau in vitro at several epitopes including Thr231, Ser262/356, Ser396, Ser409 and Ser422, whereas Ser199, Ser202, Ser235, Ser400, and Ser404 are not phosphorylated by AMPK	Mus musculus C57BL6	ADP + O-phospho-[tau-protein]	-	?

Synonyms

Synonyms	Comment	Organism
AMP-activated protein kinase	-	Mus musculus
AMPK	-	Mus musculus
tau kinase	-	Mus musculus

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Mus musculus

General Information

General Information	Comment	Organism
malfunction	AMPK inhibition leads to a rapid decrease of tau phosphorylation. AMP-activated protein kinase (AMPK) is deregulated in the Alzheimer's disease brain where it co-localized with phosphorylated tau in pre-tangle and tangle bearing neurons. AMPK mice deficient for one of the catalytic alpha subunits display reduced endogenous tau phosphorylation. AMPK deficiency reduces tau pathology in the PS19 mouse model of tauopathy	Mus musculus
physiological function	AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo. Tau functions, which include the regulation of microtubules dynamics, are dependent on its phosphorylation status, any changes in tau phosphorylation can have major impacts on synaptic plasticity and memory. Endogenous AMPK activation in mouse primary neurons induces an increase of tau at multiple sites. 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 Alzheimer's disease pathology. The two alpha subunits of AMPK can have distinct roles. AMPKalpha2, which is the most highly expressed of the catalytic subunit in the brain, is responsible for the detrimental effects observed following ischemic stroke in mice. AMPK activation increases tau phosphorylation in primary neurons and affects tau binding to microtubules. AMPK controls basal tau phosphorylation levels	Mus musculus

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Release 2023.1 (January 2023)