SUMOylation: Novel Neuroprotective Approach for Alzheimer’s Disease?

Hoppe, Juliana Bender; Salbego, Christianne Gazzana; Cimarosti, Helena

doi:10.14336/ad.2014.1205

Cited by 38 publications

(31 citation statements)

References 53 publications

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“…This occurs through the regulation of some of the most fundamental metabolic processes, including energy and nucleotide metabolism, and permits physiological adaptation in response to cellular and environmental queues (Enserink 2015; Makhnevych et al 2009). SUMO has been implicated in complex human diseases and developmental anomalies that are also associated with nutritional and/or metabolic perturbations including Alzheimer’s disease (Dorval and Fraser 2007; Hoppe et al 2015; Lee et al 2013, 2014b; Martins et al 2016; McMillan et al 2011; Sarge and Park-Sarge 2009), Parkinson’s disease (Guerra de Souza et al 2016) (Eckermann 2013; Krumova et al 2011), type I diabetes (Li et al 2005; Wang and She 2008), familial partial lipodystrophy (Simon et al 2013), diabetes-mediated cardiovascular disease (Chang and Abe 2016), congenital heart disease (Wang et al 2011), cardiomyopathy (Kim et al 2015c; Zhang and Sarge 2008), arthritis (Yan et al 2010), amyotrophic lateral sclerosis (Dangoumau et al 2016; Foran et al 2013; Niikura et al 2014), and cleft lip and/or palate (Alkuraya et al 2006; Song et al 2008; Tang et al 2014). …”

Section: 1 Introduction: Functions Of Sumo In Metabolismmentioning

confidence: 99%

The Roles of SUMO in Metabolic Regulation

Kamynina

2017

SUMO Regulation of Cellular Processes

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Protein modification with the small ubiquitin-related modifier (SUMO) can affect protein function, enzyme activity, protein-protein interactions, protein stability, protein targeting and cellular localization. SUMO influences the function and regulation of metabolic enzymes within pathways, and in some cases targets entire metabolic pathways by affecting the activity of transcription factors or by facilitating the translocation of entire metabolic pathways to subcellular compartments. SUMO modification is also a key component of nutrient- and metabolic-sensing mechanisms that regulate cellular metabolism. In addition to its established roles in maintaining metabolic homeostasis, there is increasing evidence that SUMO is a key factor in facilitating cellular stress responses through the regulation and/or adaptation of the most fundamental metabolic processes, including energy and nucleotide metabolism. This review focuses on the role of SUMO in cellular metabolism and metabolic disease.

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Section: 1 Introduction: Functions Of Sumo In Metabolismmentioning

confidence: 99%

The Roles of SUMO in Metabolic Regulation

Kamynina

2017

SUMO Regulation of Cellular Processes

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“…Alzheimer’s disease is characterized by the formation of neurofibrillary tangles and amyloid-beta (Aβ)-containing plaques. Two proteins closely associated with these features, amyloid precursor protein (APP) and tau, have recently been identified as targets of SUMOylation (Hoppe et al, 2015). Their improper SUMOylation could contribute to misfolding and aggregation (Flotho and Melchior, 2013).…”

Section: Discussionmentioning

confidence: 99%

SUMOylation of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Increases Surface Expression and the Maximal Conductance of the Hyperpolarization-Activated Current

Parker

Welch

Forster

et al. 2017

Front. Mol. Neurosci.

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Small Ubiquitin-like Modifier (SUMO) is a ∼10 kDa peptide that can be post-translationally added to a lysine (K) on a target protein to facilitate protein–protein interactions. Recent studies have found that SUMOylation can be regulated in an activity-dependent manner and that ion channel SUMOylation can alter the biophysical properties and surface expression of the channel. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel surface expression can be regulated in an activity-dependent manner through unknown processes. We hypothesized that SUMOylation might influence the surface expression of HCN2 channels. In this manuscript, we show that HCN2 channels are SUMOylated in the mouse brain. Baseline levels of SUMOylation were also observed for a GFP-tagged HCN2 channel stably expressed in Human embryonic kidney (Hek) cells. Elevating GFP-HCN2 channel SUMOylation above baseline in Hek cells led to an increase in surface expression that augmented the hyperpolarization-activated current (Ih) mediated by these channels. Increased SUMOylation did not alter Ih voltage-dependence or kinetics of activation. There are five predicted intracellular SUMOylation sites on HCN2. Site-directed mutagenesis indicated that more than one K on the GFP-HCN2 channel was SUMOylated. Enhancing SUMOylation at one of the five predicted sites, K669, led to the increase in surface expression and Ih Gmax. The role of SUMOylation at additional sites is currently unknown. The SUMOylation site at K669 is also conserved in HCN1 channels. Aberrant SUMOylation has been linked to neurological diseases that also display alterations in HCN1 and HCN2 channel expression, such as seizures and Parkinson’s disease. This work is the first report that HCN channels can be SUMOylated and that this can regulate surface expression and Ih.

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“…Recently, abnormal SUMOylation has also emerged as a new feature of heart failure pathology . In addition, SUMO has been shown to regulate APP and tau and may modulate other proteins implicated in Alzheimer's disease (AD), which may be a novel neuroprotective approach for AD …”

Section: Sumo Modificationmentioning

confidence: 99%

Deciphering the SUMO code in the kidney

Yang

Zhang

Sun

2018

J Cellular Molecular Medi

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SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.

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SUMOylation: Novel Neuroprotective Approach for Alzheimer’s Disease?

Cited by 38 publications

References 53 publications

The Roles of SUMO in Metabolic Regulation

The Roles of SUMO in Metabolic Regulation

SUMOylation of the Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 Increases Surface Expression and the Maximal Conductance of the Hyperpolarization-Activated Current

Deciphering the SUMO code in the kidney

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