title: SIRT3 attenuates MPTP-induced nigrostriatal degeneration via enhancing mitochondrial antioxidant capacity.
abstract: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which is characterized by progressive degeneration of nigrostriatal dopaminergic neurons. There is a growing consensus that mitochondrial dysfunction and oxidative stress play a crucial role in PD pathogenesis. Sirtuin3 (SIRT3) is the major mitochondria NAD(+)-dependent deacetylase that acts as a regulator of mitochondrial protein function; it is essential for maintaining mitochondrial integrity. Although SIRT3 was reported to have anti-oxidative stress activity in an in vitro study, there is no explicit in vivo evidence for the involvement of SIRT3 in the etiology of PD. The present study shows that SIRT3 null mice do not exhibit motor and non-motor deficits compared with wild-type controls. However, SIRT3 deficiency dramatically exacerbated the degeneration of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. SIRT3 null mice exposed to MPTP also exhibited decreased superoxide dismutase 2, a specific mitochondrial antioxidant enzyme, and reduced glutathione peroxidase expression compared with wild-type controls. Taken together, these findings strongly support that SIRT3 has a possible role in MPTP-induced neurodegeneration via preserving free radical scavenging capacity in mitochondria.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, MA, 02111, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Carina
authors.initials: C
authors.lastname: Peritore
authors.forename: Jessica
authors.initials: J
authors.lastname: Ginsberg
authors.forename: Merve
authors.initials: M
authors.lastname: Kayhan
authors.forename: Gizem
authors.initials: G
authors.lastname: Donmez
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D056566:Sirtuin 3 / Q000172:deficiency*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; C525046:Sirt3 protein, mouse; D056566:Sirtuin 3