Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease

Liu, Lei; Peritore, Carina; Ginsberg, Jessica; Shih, Jennifer; Arun, Siddharth; Dönmez, Gizem

doi:10.1016/j.bbr.2014.12.035

Cited by 99 publications

(67 citation statements)

References 32 publications

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“…Moreover, it has been also demonstrated that Sirt5 can be co-localized with cytochrome C controlling its acetylation levels, thus, Sirt5 would be critical for oxidative metabolism in response to stress, as well as regulating the initiation of apoptosis [62]. The importance of Sirt5 in the preservation of mitochondrial function has been highlighted in an MPTP-induced model of PD, where the absence of Sirt5 expression exacerbated the nigrostriatal dopaminergic degeneration induced by MPTP [23]. Other studies have also revealed that Sirt5 can be considered a major component of metabolic adaptivity, via a role in the regulation of detoxification processes (i.e., removal of excess ammonia produced when amino acids are used as a source of energy during fasting, caloric restriction, or high-protein diet) and in the regulation of autophagy and mitophagy [63,64].…”

Section: Discussionmentioning

confidence: 99%

“…The brain has the highest energy requirement in the body in order to maintain its functionality, thus, the activity of sirtuin family members may provide a critical link between cellular metabolism, cellular damage responses and, hence, aging in the brain [21,22]. In support of such a hypothesis, Sirt5, in particular, has been reported to act as a neuroprotective agent against motor deficit and dopaminergic degeneration in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of Parkinson’s disease [23]. Sirt6 also appears to act differentially in the brain in comparison to other organs.…”

Section: Introductionmentioning

confidence: 99%

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Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Khojah

Payne

McGuinness

et al. 2016

Cells

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There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson’s disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Khojah

Payne

McGuinness

et al. 2016

Cells

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“…In contrast, SIRT5 has robust desuccinylation, demalonylation and deglutarylation activities in vitro and in vivo, ∼1,000-fold higher catalytic efficiency than deacetylation activity . Many studies also revealed that SIRT5 plays crucial roles in the regulation of ammonia detoxification (Nakagawa et al, 2009;Polletta , 2015), fatty acid oxidation (Park et al, 2013;Zhang et al, 2015), cellular respiration (Li et al, 2015a;Park et al, 2013), ketone body formation (Rardin et al, 2013), and reactive oxygen species (ROS) management , and disregulation or uncontrolled activation of SIRT5 can cause several human diseases, for instance cancer, Alzheimer's disease, and Parkinson's disease (Kumar and Lombard, 2015;Lai et al, 2013;Liu et al, 2015;Lu et al, 2014;Parihar et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors

Yang

et al. 2016

Sci. China Life Sci.

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Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD + )-dependent protein deacetylases, which regulate important biological processes ranging from apoptosis, age-associated pathophysiologies, adipocyte and muscle differentiation, and energy expenditure to gluconeogenesis. Very recently, sirtuin 5 (SIRT5) has received considerable attention due to that it was found to have weak deacetylase activity but strong desuccinylase, demalonylase and deglutarylase activities, and it was also found to be associated with several human diseases such as cancer, Alzheimer's disease, and Parkinson's disease. In this review, we for the first time summarized the structure characteristics, known peptide and small-molecule inhibitors of SIRT5, extracted some clues from current available information and introduced some feasible, practical in silico methods, which might be useful in further efforts to develop new SIRT5 inhibitors.Sirtuin, SIRT5 inhibitor, crystal structure, small-molecule inhibitors, computer-aided drug design Citation:Yang, L., Ma, X., He, Y., Yuan, C., Chen, Q., Li, G., and Chen, X. (2017). Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors. Sci China Life Sci 60, 249-256.

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“…SIRT3 knockout significantly exacerbated nigrostriatal neuron death by MPTP (Liu et al, ; Zhang et al, ). Knockout of another mitochondrial sirtuin, SIRT5, produced a similar MPTP susceptibility, just as with SIRT3 knockout (Liu et al, ). These findings attest to the importance of acetylation level regulation in mitochondrial and neuronal health (Baeza et al, ).…”

Section: Connections Between Sirtuins and Pdmentioning

confidence: 82%

Sirtuins as modifiers of Parkinson's disease pathology

Tang

2016

J of Neuroscience Research

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Parkinson's disease (PD) is the most common movement disorder associated with the elderly which, other than symptomatic therapies, has no effective treatment or preventive measures. Sirtuins and their pharmacological activators/inhibitors have been associated with a range of neuroprotective effects, and a large body of work on sirtuins' influence on PD pathology has accumulated over the past decade. Here, evidence for sirtuins' activities as modifiers of PD pathology and how the mammalian sirtuin paralogues may have conflicting impacts on PD pathogenesis and disease progression is reviewed. The possible cellular and molecular mechanisms underlying sirtuin activities in PD are discussed in the light of current knowledge with reference to autophagy, mitochondrial homeostasis, and microtubule dynamics. © 2016 Wiley Periodicals, Inc.

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Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease

Cited by 99 publications

References 32 publications

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

Sirtuin 5: a review of structure, known inhibitors and clues for developing new inhibitors

Sirtuins as modifiers of Parkinson's disease pathology

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