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sumo alzheimer

Takuma Maruyama, Harmony Wada, Yoichiro Abe, Takako Niikura
SUMOylation, a post-translational modification of lysine residues by small ubiquitin-like modifier (SUMO) proteins, has been implicated in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD), and in neuron- and astrocyte-specific physiological functions. Global SUMOylation is increased in the AD mouse brain in the pre-plaque-forming stage but returns to wild-type levels in the plaque-bearing stage. To clarify the reason for the transient change in SUMOylation, we analyzed the alteration of global SUMOylation induced by AD-associated cytotoxic stimuli in neurons and astrocytes individually...
June 2, 2018: Biochemical and Biophysical Research Communications
Miriam A Kael, Daniel K Weber, Frances Separovic, Marc-Antoine Sani
The cleavage of the amyloid precursor protein by β- and γ-secretases is a key event in Alzheimer's disease. A fusion protein was constructed to investigate the cleavage rate and aggregation kinetics of amyloid-beta (1-40) (Aβ(1-40)) peptides. The peptide was expressed with a Small Ubiquitin-Like Modifier (SUMO) on the N-terminus and cleaved by a SUMO protease Ulp1. The time course of the cleavage reaction was monitored by SDS-PAGE gel with 100:1 or 1000:1 SUMO-Aβ(1-40) to Ulp1 molar ratio and in the presence of brain total lipid extract unilamellar vesicles...
March 9, 2018: Biochimica et Biophysica Acta
Erin Knock, Shinsuke Matsuzaki, Hironori Takamura, Kanayo Satoh, Grace Rooke, Kyung Han, Hong Zhang, Agnieszka Staniszewski, Taiichi Katayama, Ottavio Arancio, Paul E Fraser
Small ubiquitin-related modifiers (SUMOs) conjugated or bound to target proteins can affect protein trafficking, processing and solubility. SUMOylation has been suggested to play a role in the amyloid plaque and neurofibrillary tangle pathology of Alzheimer disease (AD) and related neurodegenerative diseases. The current study examines the impact of SUMO1 on processing of the amyloid precursor protein (APP) leading to the production and deposition of the amyloid-β (Aβ) peptide. An in vivo model of these pathways was developed by the generation of double transgenic mice over-expressing human SUMO1 and a mutant APP...
February 2018: Neurobiology of Disease
Robert Silvers, Michael T Colvin, Kendra K Frederick, Angela C Jacavone, Susan Lindquist, Sara Linse, Robert G Griffin
A mechanistic understanding of Aβ aggregation and high-resolution structures of Aβ fibrils and oligomers are vital to elucidating relevant details of neurodegeneration in Alzheimer's disease, which will facilitate the rational design of diagnostic and therapeutic protocols. The most detailed and reproducible insights into structure and kinetics have been achieved using Aβ peptides produced by recombinant expression, which results in an additional methionine at the N-terminus. While the length of the C-terminus is well established to have a profound impact on the peptide's aggregation propensity, structure, and neurotoxicity, the impact of the N-terminal methionine on the aggregation pathways and structure is unclear...
September 12, 2017: Biochemistry
Chih Chieh Tao, Wei Lun Hsu, Yun Li Ma, Sin Jhong Cheng, Eminy Hy Lee
Amyloid-β (Aβ) produces neurotoxicity in the brain and causes neuronal death, but the endogenous defense mechanism that is activated on Aβ insult is less well known. Here we found that acute Aβ increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Aβ induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. Knockdown of PIAS1 decreases endogenous HDAC1 SUMOylation and blocks Aβ induction of Mcl-1. Sumoylated HDAC1 reduces it association with CREB, increases CREB binding to the Mcl-1 promoter and mediates Aβ induction of Mcl-1 expression...
April 2017: Cell Death and Differentiation
Serena Marcelli, Elena Ficulle, Filomena Iannuzzi, Enikö Kövari, Robert Nisticò, Marco Feligioni
Synaptic dysfunction has been recognized as an early feature occurring at the onset of Alzheimer's disease (AD). Compromised neurotransmission leads over time to synaptic loss and these events correlate with the cognitive decline that progressively affects AD patients.Protein SUMOylation (Small Ubiquitin-like MOdifier) is a post-translational modification (PTM) involved in several cellular processes including synaptic transmission.We here demonstrate that cortical synaptosomes prepared from Tg2576 mice of 6 months of age show an increased SUMO-1ylation, which returns back to normal levels at 20 months although synaptic SUMOylation, at this age, resulted more sensible to KCl stimulus...
October 13, 2016: Molecular Neurobiology
Ivo A Hendriks, Alfred C O Vertegaal
Small ubiquitin-like modifiers (SUMOs) are essential for the regulation of several cellular processes and are potential therapeutic targets owing to their involvement in diseases such as cancer and Alzheimer disease. In the past decade, we have witnessed a rapid expansion of proteomic approaches for identifying sumoylated proteins, with recent advances in detecting site-specific sumoylation. In this Analysis, we combined all human SUMO proteomics data currently available into one cohesive database. We provide proteomic evidence for sumoylation of 3,617 proteins at 7,327 sumoylation sites, and insight into SUMO group modification by clustering the sumoylated proteins into functional networks...
September 2016: Nature Reviews. Molecular Cell Biology
Jianhua Jia, Liuxia Zhang, Zi Liu, Xuan Xiao, Kuo-Chen Chou
MOTIVATION: Sumoylation is a post-translational modification (PTM) process, in which small ubiquitin-related modifier (SUMO) is attaching by covalent bonds to substrate protein. It is critical to many different biological processes such as replicating genome, expressing gene, localizing and stabilizing proteins; unfortunately, it is also involved with many major disorders including Alzheimer's and Parkinson's diseases. Therefore, for both basic research and drug development, it is important to identify the sumoylation sites in proteins...
October 15, 2016: Bioinformatics
Frauke Liebelt, Alfred C O Vertegaal
Cellular proteomes are continuously undergoing alterations as a result of new production of proteins, protein folding, and degradation of proteins. The proper equilibrium of these processes is known as proteostasis, implying that proteomes are in homeostasis. Stress conditions can affect proteostasis due to the accumulation of misfolded proteins as a result of overloading the degradation machinery. Proteostasis is affected in neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and multiple polyglutamine disorders including Huntington's disease...
August 1, 2016: American Journal of Physiology. Cell Physiology
Myung-Jin Mun, Jin-Ho Kim, Ji-Young Choi, Min-Seon Kim, Won-Cheoul Jang, Jung Jae Lee, Young Lee Eun, Shang-June Kwak, Ki Woong Kim, Seok Bum Lee
Sumoylation regulates transcription factor transactivation, protein-protein interactions, and appropriate subcellular localization of certain proteins. Previous studies have shown that sumoylation of amyloid precursor protein (APP) is associated with decreased levels of amyloid beta (Aβ) proteins, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between polymorphisms of the SUMO genes and the risk of AD. Our study subjects consisted of 144 AD patients and 335 healthy controls without dementia...
May 15, 2016: Journal of the Neurological Sciences
Wagner Carbolin Martins, Carla Inês Tasca, Helena Cimarosti
SUMO (small ubiquitin-like modifier) conjugation is a critically important control process in all eukaryotic cells, because it acts as a biochemical switch and regulates the function of hundreds of proteins in many different pathways. Although the diverse functional consequences and molecular targets of SUMOylation remain largely unknown, SUMOylation is becoming increasingly implicated in the pathophysiology of Alzheimer's disease (AD). Apart from the central SUMO-modified disease-associated proteins, such as amyloid precursor protein, amyloid β, and tau, SUMOylation also regulates several other processes underlying AD...
March 2016: Neurochemical Research
Linda Lee, Elena Dale, Agnes Staniszewski, Hong Zhang, Faisal Saeed, Mikako Sakurai, Mauro Fa', Ian Orozco, Francesco Michelassi, Nsikan Akpan, Helaina Lehrer, Ottavio Arancio
No abstract text is available yet for this article.
2015: Scientific Reports
Linda Lee, Elena Dale, Agnes Staniszewski, Hong Zhang, Faisal Saeed, Mikako Sakurai, Mauro Fa', Ian Orozco, Francesco Michelassi, Nsikan Akpan, Helena Lehrer, Ottavio Arancio
Learning and memory and the underlying cellular correlate, long-term synaptic plasticity, involve regulation by posttranslational modifications (PTMs). Here we demonstrate that conjugation with the small ubiquitin-like modifier (SUMO) is a novel PTM required for normal synaptic and cognitive functioning. Acute inhibition of SUMOylation impairs long-term potentiation (LTP) and hippocampal-dependent learning. Since Alzheimer's disease (AD) prominently features both synaptic and PTM dysregulation, we investigated SUMOylation under pathology induced by amyloid-β (Aβ), a primary neurotoxic molecule implicated in AD...
2014: Scientific Reports
Hong-Bin Luo, Yi-Yuan Xia, Xi-Ji Shu, Zan-Chao Liu, Ye Feng, Xing-Hua Liu, Guang Yu, Gang Yin, Yan-Si Xiong, Kuan Zeng, Jun Jiang, Keqiang Ye, Xiao-Chuan Wang, Jian-Zhi Wang
Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1)...
November 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
Robert Nisticò, Caterina Ferraina, Veronica Marconi, Fabio Blandini, Lucia Negri, Jan Egebjerg, Marco Feligioni
Alzheimer's disease (AD) is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP, and JNK, are in fact subject to protein SUMO modifications or interactions...
2014: Frontiers in Pharmacology
Hannah A Davies, Mark C Wilkinson, Robert P Gibson, David A Middleton
The 50-amino acid protein medin is the main fibrillar component of human aortic medial amyloid (AMA), the most common form of localised amyloid which affects 97% of Caucasians over the age of 50. Structural models for several amyloid assemblies, including the Alzheimer's amyloid-β peptides, have been defined from solid-state nuclear magnetic resonance (SSNMR) measurements on (13)C- and (15)N-labelled protein fibrils. SSNMR-derived structural information on fibrillar medin is scant, however, because studies to date have been restricted to limited measurements on site-specifically labelled protein prepared by solid-phase synthesis...
June 2014: Protein Expression and Purification
Linda Lee, Mikako Sakurai, Shinsuke Matsuzaki, Ottavio Arancio, Paul Fraser
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and is the most common cause of dementia in the elderly. Histopathologically, AD features insoluble aggregates of two proteins in the brain, amyloid-β (Aβ) and the microtubule-associated protein tau, both of which have been linked to the small ubiquitin-like modifier (SUMO). A large body of research has elucidated many of the molecular and cellular pathways that underlie AD, including those involving the abnormal Aβ and tau aggregates...
December 2013: Neuromolecular Medicine
Xiao-Yan Zhao, Dan-Dan Wang, Ye Shan, Cui-Qing Zhu
Small ubiquitin-related modifiers (SUMOs) belong to an important class of ubiquitin like proteins. SUMOylation is a post-translational modification process that regulates the functional properties of many proteins, among which are several proteins implicated in neurodegenerative diseases. This study was aimed to investigate the changes of SUMO-1 expression and modification, and the relationship between SUMO-1 and Alzheimer's disease (AD) pathology in APP/PS1 transgenic AD mice. Using Western blot, co-immunoprecipitation and immunofluorescent staining methods, the SUMO-1 expression and modification and its relation to tau, amyloid precursor protein (APP) and β-amyloid protein (Aβ) in the 12-month-old APP/PS1 transgenic AD mice were analyzed...
June 25, 2013: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Juliana B Hoppe, Marcus Rattray, Henry Tu, Christianne G Salbego, Helena Cimarosti
Astrocyte reactivity is implicated in the neuronal loss underlying Alzheimer's disease. Curcumin has been shown to reduce astrocyte reactivity, though the exact pathways underlying these effects are incompletely understood. Here we investigated the role of the small ubiquitin-like modifier (SUMO) conjugation in mediating this effect of curcumin. In beta-amyloid (Aβ)-treated astrocytes, morphological changes and increased glial fibrillary acidic protein (GFAP) confirmed reactivity, which was accompanied by c-jun N-terminal kinase activation...
June 24, 2013: Neuroscience Letters
Laura Campello, Julián Esteve-Rudd, Nicolás Cuenca, José Martín-Nieto
The ubiquitin-proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease...
April 2013: Molecular Neurobiology
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