Emerging Role of Sirtuin 2 in Parkinson’s Disease

Liu, Yumei; Zhang, Yingying; Zhu, Konghua; Song, Chen; Wang, Chong; Xie, Anmu

doi:10.3389/fnagi.2019.00372

Cited by 57 publications

(44 citation statements)

References 131 publications

(163 reference statements)

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“…Based on previous findings of SIRT2 over-expression inducing dopaminergic cell death while enzyme inhibition exerting neuroprotective effects, it was concluded that elevated SIRT2 levels contribute to higher PD risk. In contrast to previous studies reporting on SIRT2 effects on microtubule stability, formation of alpha-synuclein aggregation, neuroinflammation and autophagy 39 our results do not support the role of SIRT2 in PD.…”

Section: Discussioncontrasting

confidence: 99%

Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

Maszlag-Török

Boros

Vécsei

et al. 2021

Sci Rep

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Parkinson’s disease (PD) is a neurodegenerative disease caused by complex interaction between genetic and environmental factors. There is a growing body of evidence of the involvement of sirtuins (SIRTs) in disease pathomechanism. SIRTs are NAD+-dependent histone deacetylases which take part in various cellular functions. However, available data of the relationship between SIRT gene polymorphisms and PD is limited. Our aim was to investigate the possible association of 10 SNPs identified within non-mitochondrial SIRTs, SIRT1, -2 and -6 with the risk of PD in Hungarian population, and to compare the expression level of these SIRTs between healthy controls and PD patients. Our results showed that rs3740051 and rs3818292 of SIRT1 and rs350843, rs350844, rs107251, rs350845 and rs350846 of SIRT6 show weak association with PD risk. On the contrary rs12778366 and rs3758391 of SIRT1 and rs10410544 of SIRT2 did not show association with PD. Moreover, we detected that mRNA level of SIRT1 was down-regulated, and mRNA level of SIRT6 was up-regulated, while SIRT2 mRNA level was not altered in the peripheral blood of PD patients as compared to controls. The difference in both cases was more pronounced when comparing the early-onset PD group to the control cohort. Nevertheless, mRNA level changes did not show any association with the presence of any of the investigated SNPs either in the PD or in the control group. In conclusion, our findings suggest that non-mitochondrial sirtuins, SIRT1 and -6 but not SIRT2 might contribute to the pathogenesis of PD in the Hungarian population both via their altered mRNA levels and via gene alterations identified as specific SNPs.

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Section: Discussioncontrasting

confidence: 99%

Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

Maszlag-Török

Boros

Vécsei

et al. 2021

Sci Rep

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“…PD not only does reduce the patient's quality of life but also brings a heavy economic burden to society and families ( 49 , 50 ). Balance dysfunction is the main reason for the increase in individuals' disability rates with PD and the decreased health-related quality of life and survival ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

A Mobile Phone App-Based Tai Chi Training in Parkinson's Disease: Protocol for a Randomized Controlled Study

et al. 2021

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Introduction: With an increasing number of China's aging population, Parkinson's disease (PD) increases year by year. Persons with PD exhibit abnormal balance functions, leading to motor skills difficulties, such as unstable walking or even falling. Therefore, activities of daily living and quality of life are affected. This study aims to explore the effectiveness of Tai Chi training based on the mobile phone app in improving the balance ability of persons with PD.Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. One hundred forty-four persons with PD who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio: (1) control group, (2) basic experimental group (basic app with no Tai Chi training features), and (3) balanced-enhanced experimental group (basic app with Tai Chi training features). Individuals with PD will be evaluated on balance and motor function outcomes. The primary outcome measure is the limits of stability (including the maximum excursion and direction control); the secondary outcome measures include the Unified Parkinson's Disease Rating Scale III (UPDRS-III), Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up & Go (TUG), 6-Minute Walk Test (6MWT), and 39-item Parkinson's Disease Questionnaire (PDQ-39). Each group of patients will go through an assessment at baseline, 17 and 33 weeks.Discussion: This study will evaluate the effectiveness of the mobile phone app Tai Chi training on the balance function of persons with PD. We assume that a challenging Tai Chi project based on a mobile phone app will improve balance in the short and long term. As walking stability progresses, it is expected that daily activities and quality of life improve. These findings will be used to improve the effectiveness of future home management measures for persons with PD.Ethics and Dissemination: This study has been approved by the ethical review committee of the Shanghai University of Sport (approval number: 102772019RT056). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published.Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000029135).

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“…SIRT2 has been reported to mediate α-Syn protein aggregation which also induces oxidative stress, in turn, leading to PD pathogenesis ( de Oliveira et al, 2017 ; Liu et al, 2020 ; Singh et al, 2017b ). SIRT2 by deacetylating FOXO3a has been shown to increase antioxidant defense mechanisms.…”

Section: Sirt1 and Sirt2 In Parkinson’s Diseasementioning

confidence: 99%

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases

2021

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Sirtuins are NAD+ dependent histone deacetylases (HDAC) that play a pivotal role in neuroprotection and cellular senescence. SIRT1-7 are different homologs from sirtuins. They play a prominent role in many aspects of physiology and regulate crucial proteins. Modulation of sirtuins can thus be utilized as a therapeutic target for metabolic disorders. Neurological diseases have distinct clinical manifestations but are mainly age-associated and due to loss of protein homeostasis. Sirtuins mediate several life extension pathways and brain functions that may allow therapeutic intervention for age-related diseases. There is compelling evidence to support the fact that SIRT1 and SIRT2 are shuttled between the nucleus and cytoplasm and perform context-dependent functions in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). In this review, we highlight the regulation of SIRT1 and SIRT2 in various neurological diseases. This study explores the various modulators that regulate the activity of SIRT1 and SIRT2, which may further assist in the treatment of neurodegenerative disease. Moreover, we analyze the structure and function of various small molecules that have potential significance in modulating sirtuins, as well as the technologies that advance the targeted therapy of neurodegenerative disease.

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Emerging Role of Sirtuin 2 in Parkinson’s Disease

Cited by 57 publications

References 131 publications

Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

Gene variants and expression changes of SIRT1 and SIRT6 in peripheral blood are associated with Parkinson’s disease

A Mobile Phone App-Based Tai Chi Training in Parkinson's Disease: Protocol for a Randomized Controlled Study

SIRT1 and SIRT2 Activity Control in Neurodegenerative Diseases

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