Table 3.
Sirtuins and neurodegenerative diseases
| Disease | Experimental settings | Result | Mechanism | References |
|---|---|---|---|---|
| Ischemia | Res in rat global | + | Increased SIRT1 activity; decrease UCP2 |
Raval, 2006; Della-Morte, 2009 |
| Res, sirtinol and SIRT1 OE in NO exposure |
+ | Increased SIRT1 activity; | Chong, 2008 | |
| SIRT1 KO in mouse focal | + | Nampt stimulates SIRT1, SIRT1 deacetylates LKB1, LKB activates AMPK |
Wang, 2011 | |
| SIRT1 Tg in mouse focal | +/− | SIRT1 overexpression | Kakefuda, 2009 | |
| Focal in rat and mouse | + | SIRT1 mediates protection of leptin, icariin and tetrahydroxystilbene glucoside |
Wang, 2009a; Wang, 2009c; Avraham, 2010; Zhu, 2010 |
|
| WD | Axonal injury in Wlds mice | + | NMNAT increases NAD+ and activates SIRT1 |
Araki , 2004; Sasaki, 2009; Babetto, 2010 |
| Retinal injury | Res in antibody-induced apotosis |
+ | Upreguates SIRT1 expression | Anekonda, 2008 |
| SIRT1 KO mice | +? | Reduced retinal cell numbers | Cheng, 2003 | |
| AD | SIRT1 KO enhances tau acetyaltion and tauopathy |
+? | SIRT1 deacetylates tau and promotes tau degradation |
Min, 2010 |
| CR in mice increases SIRT1 and reduces Aβ neuropathy |
+ | SIRT1 inhibits ROCK1 and activates α- secrease |
Qin, 2006b | |
| SIRT1 OE suppress Aβ production in mice |
+ | SIRT1 stimulate RAR and upregulates α- secrease |
Donmez, 2010 | |
| PD | SIRT1 OE in neuron after mutant α-synuclein transfection |
+ | SIRT1 activates PGC-1 and increases mitochondrial density |
Wareski, 2009 |
| Res in mice or SK-N-BE cells | + | Res stimulates SIRT1 | Albani, 2009; Chao, 2008 | |
| Res in midbrain slice | + | SIRT1 deacetylates p53 | Okawara, 2007 | |
| MPTP-induced PD model in SIRT1 tg mice |
+/− | Kakefuda, 2009 | ||
| SIRT2 inhibition in Drosophila model of PD |
− | Outeiro, 2007 | ||
| HD | Res or SIRT1 OE in neurons after mutant huntingtin transfection |
+ | SIRT1 activates PGC-1 and increases mitochondrial density |
Parker, 2005; Wareski, 2009 |
| Res in HD mice | +/− | Ho, 2010 | ||
| Sir2 inhibition in Drosophila or striatal neuronal models of HD |
− | SIRT2 inhibition decreases sterol biosynthesis |
Pallos, 2008; Luthi-Carter, 2010 | |
| Prion disease | Res or SIRT1 OE in neurons infected with mutant prion |
+ | Bizat, 2010; Seo, 2011 | |
| ALS | Res or SIRT1 OE in a mouse model of ALS |
+ | SIRT1 deacetylates p53 | Kim, 2007; Markert, 2010 |
| MS | SIRT1 activation in a mouse model of MS |
+ | Shindler, 2007; Shindler, 2010 |
Signs abbreviation used in the table: +, protective; −, detrimental; +/−, neither protective nor detrimental; Aβ, beta amyloid; ALS, amyotrophic lateral sclerosis; CR, calorie restriction; Drosophila nicotinamidase (DN); KO, knockout; MCAO, middle cerebral artery occlusion; MS, multiple sclerosis; NO, nitric oxide; OE, overexpression; OGD, oxygen-glucose deprivation; Res, resveratrol; ROCK1, Rho-associated, coiled-coil containing protein kinase 1; Tg, transgenic; UCP2, uncoupling protein 2; WD, Wallerrian degeneration.