Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

Gatta, Nicola Gaetano; Cammarota, Gaetano; Gentile, Vittorio

doi:10.3934/biophy.2016.4.529

Cited by 4 publications

(2 citation statements)

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“…Even if the oral pellicle formation may be partially mediated by hydrophobic interactions to the epithelial cell surface, the enzymatic activity of the family of transglutaminases (TGs) plays a leading role in the formation of this protein network. − TGs generate a cross-link between two peptide chains, typically between a lysine residue acting as lone-pair donor and a glutamine residue, the lone-pair acceptor, and the reaction is accomplished by the loss of an ammonia molecule. , TGs are commonly divided into nine classes, but the principal TG active in the oral cavity is transglutaminase-2 (TG-2), together with TG-1 and TG-3. TG-2 is a Ca 2+ -dependent enzyme, negatively modulated by GTP − and affected by the reversible formation of an intramolecular disulfide bridge. ,, TG-2 is released by the epithelial oral cells and plays a relevant role in the formation of the “protein pellicle”. ,− It was demonstrated that acidic-proline-rich proteins, statherin, the major histatins, and mucins are substrates of oral TG-2, and they participate in cross-linking reactions as putative pellicle precursor proteins. ,− , It has been already established by our research group that TG-2 can generate cyclo-statherin in vitro and in vivo, involving the unique K 6 residue and almost specifically Q 37 , with Q 39 as a minor secondary residue …”

Section: Introductionmentioning

confidence: 93%

“…TG-2 is a Ca 2+ -dependent enzyme, negatively modulated by GTP 16−21 and affected by the reversible formation of an intramolecular disulfide bridge. 14,22,23 TG-2 is released by the epithelial oral cells and plays a relevant role in the formation of the "protein pellicle". 6,24−26 It was demonstrated that acidic-proline-rich proteins, statherin, the major histatins, and mucins are substrates of oral TG-2, and they participate in cross-linking reactions as putative pellicle precursor proteins.…”

Section: ■ Introductionmentioning

confidence: 99%

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Mapping of Transglutaminase-2 Sites of Human Salivary Small Basic Proline-Rich Proteins by HPLC–High-Resolution ESI–MS/MS

et al. 2019

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Because of the distinctive features of the oral cavity, the determination of the proteins involved in the formation of the “oral protein pellicle” is demanding. The present study investigated the susceptibility of several human basic proline-rich peptides, named P-H, P-D, P-F, P-J, and II-2, as substrates of transglutaminase-2. The reactivity of the P-C peptide and statherin was also investigated. Peptides purified from human whole saliva were incubated with the enzyme in the presence or in the absence of monodansyl-cadaverine. Mass spectrometry analyses of the reaction products highlighted that P-H and P-D (P32 and A32 variants) were active substrates, II-2 was less reactive, and P-F and P-J showed very low reactivity. P-C and statherin were highly reactive. All of the peptides formed cyclo derivatives, and only specific glutamine residues were involved in the cycle formation and reacted with monodansyl-cadaverine: Q29 of P-H, Q37 of P-D, Q21 of II-2, Q41 of P-C, and Q37 of statherin were the principal reactive residues. One or two secondary glutamine residues of only P-H, P-D P32, P-C, and statherin were hierarchically susceptible to the reaction with monodansyl-cadaverine. MS and MS/MS data were deposited to the ProteomeXchange Consortium () via the PRIDE partner repository with the data set identifier PXD014658.

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Section: Introductionmentioning

confidence: 93%

Section: ■ Introductionmentioning

confidence: 99%

Mapping of Transglutaminase-2 Sites of Human Salivary Small Basic Proline-Rich Proteins by HPLC–High-Resolution ESI–MS/MS

et al. 2019

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Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease

Labandeira

Pedrosa

Quijano

et al. 2022

npj Parkinsons Dis.

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The role of autoimmunity in neurodegeneration has been increasingly suggested. The renin-angiotensin system (RAS) autoantibodies play a major role in several peripheral inflammatory processes. Dysregulation of brain RAS has been involved in neuroinflammation and neurodegeneration. We aimed to know whether angiotensin type-1 receptor (AT1) autoantibodies (AT1 agonists) and angiotensin-converting enzyme 2 (ACE2) autoantibodies (ACE2 antagonists) may be involved in Parkinson’s disease (PD) progression and constitute a new therapeutical target. Both AT1 and ACE2 serum autoantibodies were higher in a group of 117 PD patients than in a group of 106 controls. Serum AT1 autoantibodies correlated with several cytokines, particularly Tumor Necrosis Factor Ligand Superfamily Member 14 (TNFSF14, LIGHT), and 27-hydroxycholesterol levels. Serum ACE2 autoantibodies correlated with AT1 autoantibodies. Both autoantibodies were found in cerebrospinal fluid (CSF) of four PD patients with CSF samples. Consistent with the observations in patients, experimental dopaminergic degeneration, induced by 6-hydroxydopamine, increased levels of autoantibodies in serum and CSF in rats, as well as LIGHT levels and transglutaminase activity in rat substantia nigra. In cultures, administration of AT1 autoantibodies enhanced dopaminergic neuron degeneration and increased levels of neuroinflammation markers, which was inhibited by the AT1 antagonist candesartan. The results suggest dysregulation of RAS autoantibodies as a new mechanism that can contribute to PD progression. Therapeutical strategies blocking the production, or the effects of these autoantibodies may be useful for PD treatment, and the results further support repurposing AT1 blockers (ARBs) as treatment against PD progression.

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Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases

et al. 2021

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Context A gluten-free diet (GFD) is the recommended treatment for gluten-dependent disease. In addition, gluten withdrawal is popular and occasionally is suggested as a treatment for other autoimmune diseases (ADs). Objective The current systematic review summarizes those entities and discusses the logic behind using a GFD in classical non–gluten-dependentADs. Data Sources A search for medical articles in PubMed/MEDLINE, Web of Sciences, LILACS, and Scielo published between 1960 and 2020 was conducted, using the key words for various ADs and GFDs. Data Exxtraction Eight-three articles were included in the systematic review (using PRISMA guidelines). Data Analysis Reduction in symptoms of ADs after observance of a GFD was observed in 911 out of 1408 patients (64.7%) and in 66 out of the 83 selected studies (79.5%). The age of the patients ranged from 9 months to 69 years. The duration of the GFD varied from 1 month to 9 years. A GFD can suppress several harmful intraluminal intestinal events. Potential mechanisms and pathways for the action of GFD in the gut – remote organs’ axis have been suggested. Conclusion A GFD might represent a novel nutritional therapeutic strategy for classical non–gluten-dependent autoimmune conditions.

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Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

Cited by 4 publications

References 59 publications

Mapping of Transglutaminase-2 Sites of Human Salivary Small Basic Proline-Rich Proteins by HPLC–High-Resolution ESI–MS/MS

Mapping of Transglutaminase-2 Sites of Human Salivary Small Basic Proline-Rich Proteins by HPLC–High-Resolution ESI–MS/MS

Angiotensin type-1 receptor and ACE2 autoantibodies in Parkinson´s disease

Gluten-free diet can ameliorate the symptoms of non-celiac autoimmune diseases

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