Tau Protein Dementia

Tew protein dementia

Cognitive decline seems to be triggered as the tau protein increases. Frontotemporal dementia with motor neuron disease. In Sweden, vitamin B cocktails are already used to prevent dementia.

Hyperphosphorylization of tau protein in Down's dementia and

Alzheimer' s disease: Identification and implications in prevention and


Dau is a group of microtubule-associated protein found in neurofibrils (NFT) in the Alzheimer' s brains (AD). 39 years ago detected as a heat-stable protein that facilitated microtubules assemblage through vineyards[1], Cleveland and his colleagues showed that tau is a phosphoroprotein that in 1977 adversely modulates its capacity to induce microtubules assemblage by phosphorylation[2].

In 1986 Iqbal and Grundke found that dew was hyperphosphorylized in AD case brains and that it can cause the failure of microtubules mounting and self-mounting to twisted spiral threads, causing neurofibrillar confusion[3]. The tau/phosphorylation events are likely sequent and according to Johnson and Stoothoff and the self-association capacity of tau could be due to an unbalance in the activities of protein kinase or phosphatase (phases)[4] (Figure 1).

Dew is abnormal in phosphorylation in a group of uncommon auto-somal degradation diseases known as frontal temporal dementia with Parkinson's due to a tau genetic alteration on the 17q21 chromosome[5]. Others tauopathy includes advanced super-nuclear paralysis, chronical traumacephalopathy, Lytico-Bodig's syndrome (Parkinson's dementia syndrome of Guam), a tangle-predominant dementia, with a NFT similar to AD but without plaque.

Gangliogliomas and gangliocytomas, menses, sub-acute glaucoma, leadencephalopathy, tuberose syndrome, Hallorden sparrow's syndrome and lipofuszinosis are also referred to as tauopathies[6]. The neurofibrillar changes in all these Tauopathias consist of abnormal hyperphosphorylic Tau, indicating that this anomaly causes their dementia and denotes this, the neurological state of Tau.

International Conference on Alzheimer's and Parkinson's Disease in Florence (Italy) on Tau Patology found that neurones encircled by perineural networks with aggression seem to be immune to Tau patology and thus perineural networks can avert them. They are composed of negative-charge, sugar-containing protein, the CSPGs.

As a result, some scientists have now concluded that the illness begins very early in their lives, with dew patology in the brain stem[10]. Early prophylaxis of tau hyperphosphoryation can therefore be more important than any treatment after diagnosis of dementia. Down Syndrome dementia with hyperphosphorylization of Tau is believed to be due to the genes that phosphorylate for the mini-brain kinasis / binary kinases kinasin and regulates tyrosin 1A (DYRK1A).

It is in the crucial area of Down's disease (DS) of genome 21, which is trebled in downs. Weigle and partner trials show that the protein Phosphorylate Tau protein and, since this protein is also part of tau protein-phosphoryylation, weigle and partner proteins contribute to neurofibrillar degeneracy and can be improved in DS patients[11].

One recent weakle over-expression in DS cerebrum is that it can lead to early neurofibrillar degradation directly by hyperphosphorylating dew and indirect by phosphorylating alternate splice factors, resulting in an mismatch between 3R-tau and 4R-tau[12]. It' not just Downs-Syndrom, where the three to four parts of the mind are hyper phosphorylated.

Igbal' s research shows that the abnormal hyperphosphorylation of Tau is able to sequester not only regular Tau but also MAP MAP1 and MAP2 and disrupt the microtubules networks supported by these proteins[13]. In some cases, similar to the process of phosphoxylation, O-GlcNAcylation (or just GlcNAcylation) takes place at the same or neighbouring locations and modulates each other.

Glc DNAcylation influences protein-protein interaction, acidity, stability as well as protein-assembly. Glc DNAcylation of protein in the signalling pathways of diabetes and contribute to disease islanders' susceptibility to Alzheimers. Slides and Hart in Johns Hopkins report that hypoglycaemia in the cerebral cortex can decrease standard dew acylation of GlcNA, which exposes kinetic receptor locations, resulting in hyperphosphorylization that causes involvement and neural death[15].

Down's disease is the most frequent cause of intellectual disability and the gene involvement in homocysteine/foliate metabolic processes play a part in the aetiology of the disease. Obeid and colleagues in Homburg Germany investigated the concentration of the metabolite associated with the DNA synthesis cycles in the young people with DS and 47 similar ages using a mathematic modell to find out more about the regulatory status of the DNA synthesis cycling.

A further methylating deficiency presumed in Down's disease is the presence of the methylenetetrahydrofolate reducase (MTHFR) family. MTHFR codes for an important molecule that is involved in the transformation of immune cells, especially homocystein into methionin. Most frequent type of genetically induced homocysteinemia results from a 677C>T-pymorphism ((NM_005957.4:c. 665C>T, rs1801133) in MTHFR.

More than 40 point changes of this genetic makeup have been detected. A previous Hobbs and staff trial showed that the results were in line with the provisional finding that MTHFR 677C-->T is more common in MTHFR 677C-->T poly-morphism in the mother of Down infertile babies than in controls, with an ODDR of 1.91 (95% CI[CI] 1.19-3.05).

You also found that the MTRR 66A -->G homozygote promoter was linked to a 2. 57-fold rise in assessed hazard (95% CI 1.33-4. 99)[19]. Hobbs and other trials that suggest the link between MTHFR genetic disorder and Down's syndrome[20] were regarded as contentious by other genetics; a 2009 Dansk trial found that the joint MTHFR 677C>T poly morphism is probably not a motherly hazard for DS in their group and that the differences to earlier trials are due to a small specimen volume or geographical variations in genetic poly morphisms that include GM food or GM food ecologies.

However, two recent trials suggest a relationship between Down's disease and MTHFR and MTRR. The year 2010 was released Folat-Gen Polymorphismus and the chance of DS Syndrom pregnancy in young female China. In MTHFR, methionin synthetase reducase (MTRR), decreased folic acid1 ( "RFC-1"), methionin synthetase (MTR), which is associated with folic acid metabolic processes, and the risks of progeny of young female patients with Down's catarrh.

You found that MTHFR 677C>T homozygogenic polymorphy was more common among pregnant women with DS than among the 3:51 supervised women. Decreased (RFC-1) was not associated with MTRR, but the gay MTRR 66A>G morphism was independent associated with a 3. 16-fold rise in assumed risk[22].

Downs-Syndrom describes the malignant version of methionin synthetaseductase. As methionin synthetase reducase (MTRR) is one of the most important regulative Enzyme in the metabolism path of Homocystein, the Polymorphismus C524T of the MTRR-Genassociation with DS was investigated. Significant distribution variations in C524T allele distribution were found between case and host dams; a reduced DS was associated with the 524TT phenotype (OR=0.34), CT+TT phenotype (OR=0.60)[23].

For the first time, Schuchmann and his colleagues showed that modified Ca2+ signals and midochondrial deficits were found in hippocampal neurones of Trisomie 16 mouse, a 1998 Down's disease model[24]. In 2010, Jang's group described shortened beta-amyloid-peptide channels found in AD plaque and Down's disease premyloidal lesions, a pilot system for an early AD study[25].

Zempel et al. further reported that Abeta oligoids cause localised Ca(2+) increase, mis-sorting of endogeneous dew in the dendrite, tau-phosphorylization, and degradation of microtubuli, mitochondria, and thorns in Alzheimer's patients. Anaconda and Quinn have reported that a targeted subset of Alzheimer' s down stream paths includes disregulation of Intracellularcium ( "Ca2+"), upregulation of caspase-split Tau and hyperphosphorylization of Tau (ptau).

The researchers found that intraneural or soluble extracorporeal A? protein kinase A ( "PKA") can induces binding to LTCC and promoting an elevated Ca2+ flow, resulting in hyper phosphorylation of dew and inhibition of autophagia, a purification system within the cell[27]. Because tau hypophosphorylation is so important in the development of Alzheimer's and tauopathy, antibodies that would inhibit the acting quinases have become important for therapeutical use.

Scientists have focused on GSK-3 such as Astra Zenica and Takeda Pharmaceutical, a GSK3 high selectivity GSK3-inhibitor that inhibits 2-methyl-5- (3-{4-[(S)-methylsulfinyl]phenyl}-1-benzofuran-5 -yl)-1,3,4-oxadiazole (MMBO), which inhibits tau-phosphorylierung and Tau patology in the hippocampus in mice. Davunetid (NAP), a murine hypophosphorylation study of Tau and a 2/3 study of tuberculosis, super-nuclear paralysis, are under study by Allon Therapeutics[29].

It bind and stabilize the cytoskeletal protein F-actin in flies and prevents a cleavage protein of mitochondria from entering the organell. A number of neurological degenerative disorders such as Parkinson's and Alzheimer's have been diagnosed with a number of Mitochondrial anomalies. In 1 mM ATP, the thin films are 4-7 nm wide, while in 10 mM ATP, the thin films seemed to produce radial interactions, focusing and torsion, and form thin films such as Paired Helicalilaments ( "PHF") insulated from the Alzheimer' s brains.

Laferla's laboratory has developed lipolysaccharide (LPS) in an infectious AD inflammation pattern, APP/PS1/tau threefold transgenetic mouse, to activating the hippocampal microglial tau hyperphosphoryation after 6month. The Harish C pant and its group on the NINDS showed that neural infection with an inhibitoric acid Kdk5 protein (CIP) selective inhibits p25/Cdk5 activities and suppresses the aberrant tau- phosphorylation in correlated neurons[33].

A number of researchers believe that AD is basically a metabolism disorder with significant and progressional disorders in the use of cerebrovascular glucose levels and the ability to respond to isoline and insulin-like factors of proliferation (IGF). Burns and Vanden Heuvel believe that these mechanism involve fast reactions such as phosphorylating processes and relatively deferred transscription.

Among diabetics 2 rat and spreadtozotocin injection of diabetes mouse, tau reduces phosphoryylation and is also associated with a decrease in JNK acidity and not of GSK3? activity[38]. However there was no indication of an effectiveness of 2 mg or 8 mg RSG XR monoclonal therapy in CNS or overall functioning in APOE-?-negative or other Alzheimer' s disease-analytical population.

As Tokutake et al. have shown, the mechanisms behind A?-induced tau hyperphosphoryylation are induced by disturbed signalling of signals from isolated tau His group has devised a novel cellular culture system to evaluate the effect of A? on physiological relevance, which is of course excreted by donated tau in receptor stem cell culture.

Based on the results of many therapeutical failure of medication to change cognitive function in Alzheimer's dementia, the proofs suggest that monotherapy is moor and that the most likely option for Down's disease is dementia prophylaxis. Recently, for example, sleeping disorders in older people and the connection with dementia have been known.

Mayen Nedergaard, University of Rochester Medical Center, New York, found that the animal species along with the other metabolite better remove from the mind while asleep. Based on real-time analysis with real-time evaluations of tetramethylammonium diffuse and two-photon imagery in living mice they showed that normal or anaesthesia is associated with a 60% gain in intrastitial volume and that intrastitial flow convection has enhanced the ? amyloid clarity while asleep. The study implied that the physiologic role of insomnia is to substantially cleanse the cerebrum from the daily debris[41].

There is a high incidence of insomnia, especially in the case of fatal insomnia, in kids with Down's disease. One recent trial investigated the connection between insomnia and cognitive function in Down's disease. Twenty nine young people and young people with Down's disease took part in the survey. Participants investigated elements of executory function that have been shown to be compromised in earlier Down's disease research.

The researchers found that people with Down's disease with higher levels of BMS also reported increasing signs of ASA. Researchers from the University of Pennsylvania showed that the pollutant Arsenit causes a significant rise in phosphorylization of several residual aminos (Thr-181, Ser-202, Thr-205, Thr-231, Ser-262, Ser-356, Ser-396 and Ser-404) in Tau, which are also hyperphosphorylized under pathologic states.

The researchers found that the arsenite-induced phosphorylation of some mutated protein, in particular R406 W, was modified at several sites of phosphorylation, suggesting that these changes may significantly influence the Tau structures in vivo[43]. Low-dosed methylmercury was investigated in Neuroblastom (NB) and SH-SY5Y neurons in a cellular cultural modell to investigate low-dose MeHg effect on cellular proliferation, cellular survivability, reaction oxigenase ( "ROS") and tau protein phosphorylation. 2.

mM) and the calpaine blocker MDL-28170 (10 ?M) have significantly reduced the effect of MeHg (50 and 100 nM) on cellular vitality and tau phosphorylation[45]. 6-Amyloid interferes with the Wnt signalling pathways and is a key neural dead factor in Alzheimer's cells.

GSK-36 has been found to be phosphorylated in the hippocampus and A? neurocortical neurones, as the Wnt signalling activity has been tragically lost[47]. A further contribution investigated the effect of Sativex®, a blend of delta-9-tetrahydrocannabinol and cannabidol, which acts on both CB1 and CB2 recipients in an overwhelming anthropogenic tauopathy tau receptor hypothesis.

Sativex® enhances phenotypic, oxidation and protein deposit after brief dosing in individuals with behavioural and pathologic abnormalities[48]. After 3 consecutive subchronic phases, CBD and WIN, a blended CB(1)/CB(2) agonist, prevented the non-learning of a spacial navigational function and the expression of cytokines in ?-amyloid-injected cats.

The researchers came to the conclusion that CBD microglia cells work in vitro and induce positive results in an in vitro AD [49] mode. Previous mention was made of the GlcN acylation of protein within the signalling path of human blood and the contribution to insurance against AD and DS dementia. Hence, the need to introduce a low glycaemic diets for the patients with down's is more than obvious.

Coeliac condition has been found to have a high incidence in Down?s disease of 5-10% in some states. One group in Naples has reported that trans-glutaminases are omnipresent protein catalyzing post-translational modificationases. The crosslinking of polyglutaminyl glutamine residue from a protein/peptide substratum to form proteinaceous residue of a protein/peptide co-substrate can be a contributor to neurologicaldegenerative disorders such as Alzheimer's, Parkinson's, super-nuclear paralysis, Huntington's and other polyglutaminic ailments.

Some of these diseases are characterised by abnormal trans-glutaminase activities and by elevated cross-linked protein levels in the affected brain[51]. In 2006, this writer and L Pearce et al. for the first time publish the application of moderately applied magnetotherapy in Alzheimer's in the Society for Neuroscience.

Investigations by Alan MacDonald MD[56] and later Judith Miklossy MD[57] have shown that Borreliaburg darferi remains in the cerebral system in the case of Lyme nuroborreliosis as the infective Alzheimer' s. The results show that Borreliaburg darferi remains in the blood. Inflammations in the shape of reaction alcytes and microglial cells are important in the development of Alzheimer's. The inflammatory processes of Alzheimer's patients with Alzheimer' s are also important.

Alzheimer' s is a neuro-degenerative disorder caused by oxidation and associated with hereditary and ecological issues such as pesticide and metal exposures, with consequent degradation of mitochondrial protections, peroxide dismutase und free radikallan. Because of its highly adverse static electricity, it can even propel Borrelia Bb (Lyme borreliosis) out of the tissue and raise the body's own hosts.

Wang and Yarema used another document that publicized and unreleased research found up-regulation of the genes for isolating factor groups, whereas peripheral receptors of proteins were elevated, and adding to the B vitamin for the inhibition of MTHFR and MTRR chromosomal protein S, as well as releasing the MTRR: A: A: A: A: A: A: A: B: A: A: A: A: A: B: A: A: A: A: A: A: A: A: A: B: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: A: B:

Preceding section on MTHFR and MTRR induced methylization errors means that the addition of methylcobalamin and a trimethylglycin (betaine) to the body inhibits gomocysteine, a poisonous amino acid, by the addition of the following thereto: L-5 -MTHF folates, pyridoxal-5 phosphorus containing vitamine and the methylcobalamin B-12 methyldonor.

In a recent clinical trial of cerebral imagery in older patients with an advanced dementia-risk ( "mildly impaired cognition" according to the 2004 Petersen criteria), a high-dose B-vitamin therapy (folic acids 0.8 mg, vitamins 20 mg, B12 0.5 mg) retarded total cerebral contraction for 2 years by reducing the increase in the level of plasm homocysteine[62].

The use of methylized types of these important amino acids can be assumed to be more efficient, as about 30% of the general public may have the genetic deficiencies listed above. Nicolia et al. also found that the lack of B-vitamins stimulates tau-phosphorylierung by regulating GSK ß and PP2A.

The researchers found that the upregulation of GSR3beta and protein phospatase 2 A (PP2A) by inhibition of myelination responses due to B-vitamin deficiencies. Numerous research issues on the hyperposphorylization of tau in down dementia have not yet been addressed, e.g. why Serin and Treonin remains (Ser/Thr) are generally chlorinated and which are chlorinated under abnormal states.

Also, why some residuals are phosphorylated early versus later in the illness and that significant residuals that are phosphorylated in patients with Down's dementia are different from Alzheimer's illness. Tus hyperphosphoryation in Down's dementia and Alzheimer's and other tauopathias has been shown with changes in signalling of island signals, calcius signalling, mitochondrial decrease and oxidation stresses.

Methylization errors in MTHFR and MTHFR gene were also under discussion. Preventing tau hypophosphorylation in Downs-Syndrom with sleeping pills is suggested. Purifying the diets to avoid high glycaemic diets and high levels of glucose is as important as consuming a high antioxidant diets and supplementing with vitamin B1 due to MTHFR and MTTRR deficiencies.

Strong anti-oxidants such as muscadin cores can be particularly important in Down's lymph. Neuroprotective agents such as CBD can turn out to be effective therapies for DS dementia and Alzheimer's ailments. Modest magnetotherapy in moderately cognitively impaired patients together with the use of antimicrobial agents such as minocyclin and doxycyclin in spirochetal-associated dementia is further proof of the emergent importance of pathogenic agents in Alzheimer's incontinence.

An infant with Down's disease should not be condemned to a later dementia because it has hereditary inheritance of TRISOMIE 21. MD Weingarten, Lockwood AH, Hwo SY, Kirschner MW (1975)A protein element that is indispensable for microtube mount. K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, et al. (1986)Defective microtubules in the brains in Alzheimer's patients.

Chrysophorylation in neural cellular functions and disorders. PORKAYP, Bird TD, Wijsman E, Nemens E, Garruto RM et al. Tau is a DNA candidates for CR 17 fronto-temporal dementia (1998) Ann Neurol;43:815-825 6th thibodeau MP, Chertkpow H, Leger GC (2009) An evolving set of tauopathy diagnostics criterions.

Alzheimer' s Iqbal K, Liu F, Gong CX, Grundke-Iqbal I (2010)Tau and related tauopathias. Alzheimer' s Braak H, Thi DR, Hebremedhin E, Del Tredici K (2011)Stages of the pathological processes in Alzheimer's: ages from 1 to 100 years. Wayiel J, Dowjat K, Kaczmarski W, Kuchna I, Nowicki K, et al. (2008)The roll of DYRK1A protein in the early occurrence of neurofibrillar degeneracy in Down's lymphoma.

Wayiel J, Kaczmarski W, Barua M, Kuchna I, Nowicki K, et al. (2011)Relationship between hyperexpression of PDYRK1A and multiple amplification of neurofibrillar degeneracy with 3-repeat tau protein in Down's disease. Wayiel J, Kaczmarski W, Barua M, Kuchna I, Nowicki K, et al. (2011)Relationship between hyperexpression of PDYRK1A and multiple amplification of neurofibrillar degeneracy with 3-repeat tau protein in Down's disease.

Slides WB, Hart GW (2007)O-GlcNAc modifications in the treatment of Alzheimer' s/Diabetics. Obid R, Hartmuth K, Herrmann W, Gortner L, Rohrer TR, et al. (2012)Blood biomarker of Down-syndrome methylation and metabolism simulation with a mathematician.

The Castro R, Rivera I, Ravasco P, Camilo ME, Jakobs C, et al. (2004)5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C changes are associated with genomiclylation. They are polymorphisms in the genes that participate in folic acid metabolic processes as motherly risks for Down's sickness.

Martinez-FrÃas ML, Pérez B, Desviat LR, Castro M, Leal F et al. (2006) Mothers' poly-morphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes: Is there a connection between Folate Polymorphisms, the females' maternal gomocysteine level and the RSI of a descendent diagnosed or dyssopantchy? Kokotas H, Grigoriadou M, Mikkelsen M, Giannoulia-Karantana A, Petersen MB (2009)Investigation of the effects of Down disease on the joint MTHFR 677C>T poly-morphism in the Danes.

and Liao YP, Bao MS, Liu CQ, Liu H, Zhang D (2010)[folate genetic polymorphism in young female in China]. Qiao FY, Wang SS, Feng L, Qiao FY, Lv JJ (2013)Functional version of methionin synthetase reducase reduces the risks of Down's disease in China. Shechmann S, Müller W, Heinemann U (1998)Modified Ca2+ signalling and alterations in renal syndrome in chromosomal cell sneurones from 16 mice of trisomy: a Down's-syndromic model.

Alzheimer' s and Down's Syndrome: Jang H, Arce FT, Ramachandran S, Capone Ru, Azimova Ru, et al. (2010)Truncated beta-amyloid protein pathways offer an alternate mechanisms for Alzheimer's and Down's Syndrom. Aneconda TS, Quinn JF (2011)Calcium canal blockade as a therapeutical therapy for Alzheimer's: the case for Isradipin. M Kitazawa M, Oddo S, Yamasaki TR, Green KN, LaFerla FM (2005)Lipopolysaccharide-induced infection worsens tau patology by a cyclin-dependent kinase-5 mediated route in a genetically modified variant of Alzheimer's. The results of this study have been presented to the public.

Acter K, Lanza EA, Martin SA, Myronyuk N, Rua M, et al. (2011)Diabetes and Alzheimer' s disease: common patology and treat? Acter K, Lanza EA, Martin SA, Myronyuk N, Rua M, et al. (2011)Diabetes and Alzheimer' s disease: common patology and treat? BURNES KA, VandenHeuvel JP (2007)Modulation of PPAR acidity by phosphorylization.

Alderton C, Zvartau-Hind M, Egginton S, Saunders AM, et al. (2010)Rosiglitazone single therapy for light to moderately severe Alzheimer's disease: Results of a randomised, double-blind, placebo-controlled pivotal clinical trial. Geriatric CognDisord 30: 131-146. YOON SY, PARK JS, CHOI JE, CHOI JM, Lee WJ, et al. (2010)Rosiglitazone decreases tau phosphorylation by JNK escapement in the hippocampal of SH-SY5Y transformed tau and SH- 2 diabetic mice.

Limit AS, Kowgier M, Yu L, Buchman AS, Bennett DA (2013)Sleep fragmentation and the risk of Alzheimer's disease and cognitive decline in the elderly. It is Xie L, Kang H, Xu Q, Chen MJ, Liao Y, et al. (2013)Sleep stimulates the elimination of metabolites from the mature mind. Åndò CC, Spanà G, Edgin JO (2013)The effects of insomnia on executives in Downâ?"s.

CASAREJO'S MJ, PERUCHO J, GOMEZ A, MUSIOZ MP, FERNANDEZ-ESTEVEZ M, et al. (2013)Natural CANABINOIDS enhance nortransmission of DOPAMIN and tau and AMYLOOID pathologies in a MICE. Aydogdu S, et al. (2003)Celiac condition in pediatric patients with Down's syndrome: importance of follow-up and serological screen.

Transglutaminase escapement as a possible therapeutic method to prevent cell death in the treatment of NET. MartÃn-Moreno AM, Reigada D, RamÃrez BG, Mechoulam R, Innamorato N, et al. (2011)Cannabidiol and other cannabinoids are reducing in vitro and in vivo cannabinoid activation: relevancy for Alzheimerâ??s Disease.

The heterogeneity of reds in polyphenols has different effects on the neuro-pathology of Alzheimer's diseases and different levels of degradation. Jadhav S, Neradil P, Madari A, et al. (2012)Who stokes the fires of the Alzheimer's brain? Alzheimer' s Braak Stage progression; re-examined and described as Borrelia infectious transfer through neuronal circuitry.

Alzheimer' s disorder - a neurological spirochetosis. douaud G, refsum H, de Jager CA, Jacoby R, Nichols TE, et al. (2013)Prevention of alzheimer's by means of B-vitaminisation. Cavallaro RA, Di Luzio A, Scarpa S (2010)B and Nicolia V, Fuso A, Scarpa S (2010)B promote tau-phosphorylierung by regulating GSK3beta and PP2A.

Auch interessant

Mehr zum Thema