Literature summary for 2.3.1.B41 extracted from

Kaluski, S.; Portillo, M.; Besnard, A.; Stein, D.; Einav, M.; Zhong, L.; Ueberham, U.; Arendt, T.; Mostoslavsky, R.; Sahay, A.; Toiber, D.
Neuroprotective functions for the histone deacetylase SIRT6 (2017), Cell Rep., 18, 3052-3062 .

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Application

Application	Comment	Organism
medicine	SIRT6 and its downstream signaling can be targeted in Alzheimer's disease and age related neurodegeneration	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	generation of brS6KO mice, phenotype, overview. Brains of brS6KO mice are significantly smaller, but otherwise structurally normal. brS6KO mice exhibit increased signs of DNA damage, marked by increased levels of ATM and H2AX phosphorylation, increased H3K56ac, and reduced SNF2H recruitment to chromatin. A significant increase in apoptotic cells in the cortex is observed, as determined by TUNEL staining in young mice (3-4 month old). SIRT6-deficient brains have increased signs of DNA damage and cell death. Behavioral defects of brS6KO mice, overview. SIRT6 deletion markedly decreases non-associative (OF) and associative (CFC) learning. SIRT6KO cells are more sensitive to apoptosis, prevented by GSK3 or ATM inhibition	Mus musculus
additional information	generation of SIRT6KO cells from SH-SY5Y cells	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-
nucleus	-	Mus musculus	5634	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q8N6T7	-	-
Mus musculus	P59941	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Mus musculus	-
brain	SIRT6 is highly expressed in human brains but reduced in Alzheimer's disease patients, SIRT6 mRNA and protein levels are reduced in patients with Alzheimer's disease in temporal cortex and hippocampus	Homo sapiens	-
hippocampus	-	Homo sapiens	-
additional information	SIRT6 and PP2A regulatory subunit (PPP2AR1A, the main Tau phosphatase) expression are positively correlated in normal brains, but this correlation is lost in Alzheimer's disease brains	Homo sapiens	-
neuron	-	Homo sapiens	-
neuron	-	Mus musculus	-
SH-SY5Y cell	-	Homo sapiens	-
temporal lobe	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
histone deacetylase	-	Homo sapiens
histone deacetylase	-	Mus musculus
SIRT6	-	Homo sapiens
SIRT6	-	Mus musculus

General Information

General Information	Comment	Organism
malfunction	SIRT6 activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 and its downstream signaling can be targeted in Alzheimer's disease and age related neurodegeneration. Patients with Alzheimer's disease show a remarkable reduction in SIRT6 at both protein and mRNA levels, with further reduction with increased severity of Braak stages. SIRT6KO cells are more sensitive to apoptosis, prevented by GSK3 or ATM inhibition	Homo sapiens
malfunction	SIRT6 activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Brain-specific SIRT6-deficient mice survive, but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death and hyperphosphorylated Tau, a critical mark in several neurodegenerative diseases	Mus musculus
physiological function	neuroprotective functions for the histone deacetylase SIRT6. SIRT6 promotes DNA repair, but its activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3alpha/beta. SIRT6 is critical to maintain genomic stability in the brain and its loss leads to toxic Tau stability and phosphorylation. SIRT6 protects the brain from naturally accumulating DNA damage, in turn protecting against neurodegeneration	Homo sapiens
physiological function	neuroprotective functions for the histone deacetylase SIRT6. SIRT6 promotes DNA repair, but its activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3alpha/beta. SIRT6 is critical to maintain genomic stability in the brain and its loss leads to toxic Tau stability and phosphorylation. SIRT6 protects the brain from naturally accumulating DNA damage, in turn protecting against neurodegeneration	Mus musculus

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Release 2023.1 (January 2023)