Laboratory of synthetic vaccines

Department of Molecular Neurobiology

Head: Olga Volpina, D.Sc, professor
volpina@ibch.ru+7(495)336-57-77

synthetic peptides, antipeptide antibodies, antiviral antibodies, antibacterial antibodies, diagnostic antibodies, immunotherapy

Laboratory develops artificial vaccines based on synthetic peptide fragments of various proteins. Work is aimed at fighting with neurodegenerative diseases, particularly Alzheimer's disease.

Researchers make antibodies to endogenous neuronal receptors to block the binding of amyloid-beta receptors. In the Laboratory such neuronal receptors asa nicotinic acetylcholine receptor, prion protein receptor, receptor for glycation end-product and neurotrophin receptor are under their investigation. Also in the Laboratory peptide drugs direct stimulating protective effects are being developed. Nowadays they have successfully managed to create a peptide RAGE-60-76 (fragment of the glycation end-product’s receptor), which shows a therapeutic effect after intranasal incertion to mice with olfactory bulbectomy (an excision of the olfactory bulb in mice leads to the development of symptoms of Alzheimer's disease).

Earlier Laboratory had created vaccines that are inactivated viral and bacterial diseases, such as foot and mouth disease, poliomyelitis, encephalitis, meningococcus, and others. In addition, researchers received antibodies to the tumor-associated proteins for the diagnosis of cancer.

Laboratory cooperates with IBCh’s laboratories, Institute of Cell Biophysics, the A.N. Belozersky Institute of Physico-Chemical Biology, with the Faculty of Biology at Moscow State University and the Institute of Higher Nervous Activity and Neurophysiology RAS, as well as with institutes in Poland, Czech Republic and other countries.

Laboratory of synthetic vaccines was founded in 2004 on the basis of synthetic vaccines Group (since 1987).

The theoretical and practical approach to creation of artificial vaccines on the basis of synthetic fragments of viral and bacterial proteins. Prediction and synthesis of immunoactive peptide fragments of endogenous proteins for induction of diagnostic and therapeutic antibodies.

  1. Creation of artificial vaccine against foot-and-mouth disease on the basis of synthetic fragments of VP1 viral protein.
  2. Induction of anti-meningitis protective immunity against A, B and C serogroups using the synthetic fragments of outer membrane proteins from Neisseria meningitides and the peptides conjugated with high-molecular capsule polysaccharides of the serogroup A meningococcus.
  3. Development of the peptide vaccine against tick-borne encephalitis on the basis of synthetic fragments of viral NS1 and E proteins
  4. Induction with synthetic peptides of polyclonal and monoclonal antibodies for diagnostics and therapy of prion diseases.
  5. Development of new approach to the immunotherapy of Alzheimer’s disease with the synthetic fragments of alpha 7 subunit of the acetylcholine receptor. Investigation of molecular mechanisms of cholinergic system action with the antibodies against synthetic fragments of alpha 7 subunit of the acetylcholine receptor.
  6. Induction of diagnostic antibodies against tumor associated proteins — nucleiphosmin and survivin, using synthetic peptides.
Laboratoty employees
NamePositionContacts
Olga Volpina, D.Sc, professordepart. dir.volpina@ibch.ru+7(495)336-57-77
Tat'jana Volkova, Ph.D.s. r. f.tdvol@mx.ibch.ru+7(495)336-57-77
Dmitri Koroev, Ph.D.s. r. f.koroev@mx.ibch.ru+7(495)3365777
Margarita Filatova, Ph.D.s. r. f.filatova07@mail.ru+7(495)336-57-77
Anna Kamyninar. f.aneskaminina@mail.ru+7(495)336-57-77
Samson Balasanyantspr. lab. as.

Former members:

Ol'ga Chibiskovaj. r. f.

Selected publications

  1. Volpina O.M., Samokhin A.N., Koroev D.O., Nesterova I.V., Volkova T.D., Medvinskaya N.I., Nekrasov P.V., Tatarnikova O.G., Kamynina A.V., Balasanyants S.M., Voronina T.A., Kulikov A.M., Bobkova N.V. (2018). Synthetic fragment of receptor for advanced glycation end products prevents memory loss and protects brain neurons in olfactory bulbectomized mice. JAD 61 (3), [+]

    Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer’s disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration. We have synthesized peptide fragments from surface-exposed regions of RAGE. Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice, which developed some characteristics similar to AD neurodegeneration. We have found that only insertion of fragment (60-76) prevents the memory of OBX mice. Immunization of OBX mice with peptides showed that again only (60-76) peptide protected the memory of animals. Both intranasal insertion and immunization decreased the amyloid-β (Aβ) level in the brain. Activity of shortened fragments of (60-76) peptide was tested and showed only the (60-70) peptide is responsible for manifestation of activity. Intranasal administration of (60-76) peptide shows most protective effect on morpho-functional characteristics of neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we revealed its penetration in the brain of OBX mice as well as colocalization of Flu-labeled peptide with Aβ in the brain regions in transgenic mice. Flu-(60-76) peptide complex with trimer of Aβ was detected by SDS-PAGE. These data indicate that Aβ can be one of the molecular target of (60-70) peptide. These findings provide a new peptide molecule for design of anti-AD drug and for investigation of RAGE activation ways in progression of AD neurodegeneration.

    ID:1949
  2. Gavrilova S.I., Volpina O.M., Kolykhalov I.V., Fedorova Y.B., Selezneva N.D., Ponomareva E.V., Koroev D.O., Kamynina A.V. (2017). [Therapeutic monitoring and prediction of the efficacy of neurotrophic treatment in patients with amnestic type of mild cognitive impairment]. Zh Nevrol Psikhiatr Im S S Korsakova 117 (8), 27–38 [+]

    To perform therapeutic monitoring and prediction of the neurotrophic therapy efficacy in patients with amnestic type of mild cognitive impairment (aMCI) in a model of course cerebrolysin therapy.

    ID:1945
  3. Koroev D.O., Volpina O.M., Volkova T.D., Kamynina A.V., Filatova M.P., Balasanyants S.M., Samokhin A.N., Bobkova N.V. (2017). A synthetic fragment 60–70 of the receptor for advanced glycation end products exhibits a therapeutic effect in an animal model of Alzheimer’s disease. Russ. J. Bioorgan. Chem. 43 (42), 150–154 [+]

    Six synthetic peptides overlapping a fragment 60-76 of the receptor for advanced glycation end products (RAGE) were studied on a protective effect on spatial memory of animals in the experimental model of Alzheimer's disease. It was shown that only a peptide corresponding to the fragment 60-70 of RAGE exhibits a therapeutic activity. Intranasal administration of this peptide into bulbectomized mice, which develop neurodegenerative features of the Alzheimer type, completely protects animal memory. Thus, it was found that the N-terminal region (60-70) within the peptide sequence 60-76 of RAGE is responsible for the revealed protective effect. The synthetic peptide RAGE-(60-70) could be the basis for the development of a new drug for the treatment of Alzheimer's disease.

    ID:1948
  4. Kolarova M., Ricny J., Bartos A., Volpina O.M., Koroev O.D., Ripova D., Kamynina A.V. (2016). Naturally occurring Antibodies against Synthetic Fragment of Neurotrophin Receptor P75 in Sera of Cognitively Impaired Patients. SOJ Immunol 4 (2), 1–4 [+]

    Aims:Alzheimer's disease is characterized by extracellular inclusions of beta-amyloid peptide. This peptide interacts with neuronal receptors in the human brain such as neurotrophin receptor P75 and neuronal acetylcholine receptor (nAChR) α7-type and pulls them down into plaques. Degraded receptors may introduce new antigenic epitopes to be recognized by specific antibodies in AD patients. The aim of the present work was to estimate the levels of the naturally occurring antibodies against two peptides derived from neuronal receptors –P75 and α7-type nAChR in sera of patients with different cognitive impairment.

    Methods: We have used short fragments from the extracellular part of each receptor that participates in the interaction with betaamyloid peptide, and measured levels of antibodies against them in the serum of different groups of patients (n = 74) by ELISA.

    Results and Conclusion: We found antibodies against the fragment of P75 receptor only. These levels tend to be higher in patients with mild cognitive impairment. This study provides findings suggesting the immunologic response to neurotrophin receptor P75 in cognitively impaired subjects.

    ID:1950
  5. Bobkova N., Vorobyov V., Medvinskaya N., Nesterova I., Tatarnikova O., Nekrasov P., Samokhin A., Deev A., Sengpiel F., Koroev D., Volpina O. (2016). Immunization Against Specific Fragments of Neurotrophin p75 Receptor Protects Forebrain Cholinergic Neurons in the Olfactory Bulbectomized Mice. J. Alzheimers Dis. 53 (1), 289–301 [+]

    Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with marked cholinergic neuron loss and amyloid-β (Aβ) peptide accumulation in the brain. The cytotoxicity in AD is mediated, at least in part, by Aβ binding with the extracellular domain of the p75 neurotrophin receptor (p75NTR), localized predominantly in the membranes of acetylcholine-producing neurons in the basal forebrain. Hypothesizing that an open unstructured loop of p75NTR might be the effective site for Aβ binding, we have immunized both olfactory bulbectomized (OBX) and sham-operated (SO) mice (n = 82 and 49, respectively) with synthetic peptides, structurally similar to different parts of the loops, aiming to block them by specific antibodies. OBX-mice have been shown in previous studies, and confirmed in the present one, to be characterized by typical behavioral, morphological, and biochemical AD hallmarks, including cholinergic deficits in forebrain neurons. Immunization of OBX- or SO-mice with KLH conjugated fragments of p75NTR induced high titers of specific serum antibodies for each of nine chosen fragments. However, maximal protective effects on spatial memory, evaluated in a Morris water maze, and on activity of choline acetyltransferase in forebrain neurons, detected by immunoreactivity to specific antibodies, were revealed only for peptides with amino acid residue sequences of 155-164 and 167-176. We conclude that the approach based on immunological blockade of specific p75NTR sites, linked with the cytotoxicity, is a useful and effective tool for study of AD-associated mechanisms and for development of highly selective therapy of cholinergic malfunctioning in AD patients.

    ID:1946
  6. Вольпина О.М., Воробьев В.В. 2, Медвинская Н.И. 2, Нестерова И.В. 2, Самохин А.Н. 2, Короев Д.О., Бобкова Н.В. 2 (2016). Иммунологический подход к структурно-функциональному картированию мембранных рецепторов. Biol Membrany 33 (5), 335–343 [+]

    Effects of the immunization against non-structural fragments of extracellular domain of p75 neurotrophin receptor (p75 NTR) containing binding sites for nervous grow factor, amyloid-beta, and pro-neurotrophin were studied. Immunization of NMRI mice with synthetic peptides with amino acid sequences corresponding to the p75 NTR fragments 86–93 and 146–153 exerted adverse effects both on the morphology of the cortical and hippocampal neurons and on spatial memory in the immunized animals. In contrast, immunization against the p75 NTR fragment 167–176 was accompanied by an improvement of these characteristics. Taken together, the results of the structural-functional mapping of the extracellular domain in neuronal membrane receptors in vivo were in line with the known X-ray data concerning the receptor structure. The developed immunological approach based on the analysis of the consequences of the immunological blockade of the receptor sites in normal and pathological conditions allows the revelation of the peculiarities in the receptor functioning in the course of the Alzheimer’s type neurodegeneration and may provide an effective way for selective therapy of the Alzheimer’s disease. Keywords: neurotrophin receptor р75 NTR, synthetic peptides, unstructured fragments of р75 NTR, active immunization, morphofunctional state of neurons, spatial memory

    ID:1968
  7. Volpina O.M., Koroev D.O., Volkova T.D., Kamynina A.V., Filatova M.P., Zaporozhskayva Y.V., Samokhin A.N., Aleksandrova I.J., Bobkova N.V. (2015). [Fragment of Receptor for Advanced Glycation End Products Improves Memory State in a Model of Alzheimer's Disease]. Bioorg. Khim. 41 (6), 709–16 [+]

    A number of synthetic peptides corresponding to potentially important regions in the sequence of the four membrane proteins known as beta-amyloid cell receptors have been investigated on their ability to improve memory state in experimental model of Alzheimer's disease. Nine fragments repeating all the exposed nonstructural regions of the RAGE protein according to X-ray data, have been synthesized. The activity of these peptides and synthesized earlier immunoprotective fragments of other three proteins (acetylcholine receptor alpha7-type, prion protein and neurotrophin receptor p75) has been investigated under intranasal administration, without immune response to the peptide. Only one fragment RAGE (60-76) was shown to have a therapeutic activity improving the memory state of bulbectomized mice and leads to decreasing in the level of brain beta-amyloid.

    ID:1947
  8. Kamynina A.V., Ponomareva E.V., Koroev D.O., Volkova T.D., Kolykhalov I.V., Selezneva N.D., Gavrilova S.I., Volpina O.M. (2015). [The reduced level of antibodies to acetylcholine receptor alpha 7 fragment in the blood serum of patients with Alzheimer's disease]. Zh Nevrol Psikhiatr Im S S Korsakova 115 (12), 128–132 [+]

    Determination of antibodies to neuronal membrane proteins in the blood serum of patients is of interest for diagnosis and optimization of treatment of Alzheimer's disease (AD). Authors studied the level of antibodies to acetylcholine receptor alpha 7 protein fragment (AChR), prion protein (РrР) and glycation end-products (RAGE) as well as to intracellular proteins nucleophosmin (Nuc) and survivin (Sur) in the serum of AD patients.

    ID:1969
  9. Бобкова Н.В. 2, Медвинская Н.И. 2, Нестерова И.В. 2, Самохин А.Н. 2, Камынина А.В., Короев Д.О., Волкова Т.Д., ЗАПОРОЖСКАЯ Я.В., Вольпина О.М. (2015). Структурно-функциональное картирование экстрацеллюлярного участка рецептора нейротрофинов р75. Biol Membrany 32 (3), 175–184 [+]

    Receptor p75 is a classical membrane receptor which consists of an extracellular region, transmembrane region and intracellular C-terminus death domain. p75 is involved in activation of neurotrophic factors and plays an essential role in regulating such cell functions as proliferation, differentiation, synaptogenesis, neuronal plasticity and survival or apoptosis. In complex with Trk receptor, p75 is believed to accelerate positive effects of neurotrophins, while in the absence of Trk receptors interaction of p75 with neurotrophins leads to cell apoptosis. In the last few years the interest to the p75 receptors has increased dramatically, as it was shown previously that p75 may play a crucial role in the genesis of neurodegenerative disorders, Alzheimer's disease in particular. Interaction of p75 with beta-amyloid leads to neuronal death in the brain. Identification of the p75 protein regions involved in the pathology is of great importance for understanding the mechanisms of the Alzheimer's disease and for the development of the target-specific treatment of this disorder. In the present work, using immunological approaches, structure-functional mapping of the extracellular domain of receptor p75 was carried out during the development of a neurodegenerative process in olfactory bulbectomized animals On the basis of X-ray data of the p75 molecule, nine extracellular receptor regions were chosen that hypothetically include beta-amyloid-binding sites and participate in the pathology progression. Peptides with the aminoacid sequences analogous to the chosen regions were synthesized. Immunization with such fragments conjugated with hemocyanin induced the formation of antipeptide antibodies in experimental animals. Of all peptides tested, only immunization with fragment (167-176) prevented the memory loss and neuronal death in the cortex and hippocampus of the bulbectomized mice. This fragment had no effect on sham-operated mice. The data obtained indicate that fragment (167-176) of the p75 sequence deserves further research as a potential basis for targeted immunotherapy of Alzheimer's disease.

    ID:1970
  10. Bobkova N.V., Medvinskaya N.I., Kamynina A.V., Aleksandrova I.Y., Nesterova I.V., Samokhin A.N., Koroev D.O., Filatova M.P., Nekrasov P.V., Abramov A.Y., Leonov S.V., Volpina O.M. (2014). Immunization with either prion protein fragment 95-123 or the fragment-specific antibodies rescue memory loss and neurodegenerative phenotype of neurons in olfactory bulbectomized mice. Neurobiol Learn Mem 107, 50–64 [+]
    ID:1382
  11. Ахидова Е.В., Волкова Т.Д., Короев Д.О., Якупов И.Ю., Завалишина Л.Э., Каплун А.П., Жарская О.О., Зацепина О.В., Вольпина О.М. (2013). Получение аффинноочищенных противопептидных антител к сурвивину для структурно-функциональных исследований белка. Биоорг. хим. 39 (3), 326–337 [+]

    Опухолеассоциированный белок сурвивин — это бифункциональный белок, который в зависимости от локализации в клетке и своего структурного состояния может участвовать либо в регуляции клеточного деления, либо в ингибировании апоптоза. Цель данной работы заключалась в получении моноспецифических антител к сурвивину, направленных к различным его участкам и пригодных для изучения структурно-функциональных особенностей белка. Изучена способность антител выявлять сурвивин в опухолевых клетках и тканях опухоли молочной железы. Показано, что наиболее высокой специфической активностью обладают антитела, направленные к участкам (1—22) и (95—105) белка. Антитела к участку (1—22) в условиях иммуноблота связываются преимущественно с сурвивинсодержащим комплексом, который, предположительно, является димером сурвивина, тогда как антитела к участку (95—105) выявляют только мономерную форму белка. Исследование образцов опухолей молочной железы показало, что мономер сурвивина присутствует только в образцах опухолевых тканей, тогда как сурвивинсодержащий комплекс экспрессируется как в опухолевых, так и в смежных с опухолью тканях. Показано, что в условиях иммуноцитохимии антитела к участку (1—22) выявляют преимущественно сурвивин ядерной локализации, участвующий в регуляции митоза, в то время как антитела к участку (95—105) дают окрашивание нуклеоплазмы и цитоплазмы на всех стадиях клеточного цикла. Таким образом, полученные антитела могут служить полезным инструментом для проведения структурно-функциональных исследований сурвивина.

    ID:1546
  12. Volpina O.M., Volkova T.D., Medvinskaya N.I., Kamynina A.V., Zaporozhskaya Y.V., Aleksandrova I.J., Koroev D.O., Samokhin A.N., Nesterova I.V., Deygin V.I., Bobkova N.V. (2009). [Protective Activity of Prion Protein Fragments after Immunization of Annimals with Experimentally Induced Alzheimer's Disease]. Bioorg. Khim. 41 (2), 145–53 [+]
    ID:1385
  13. Vol'pina O.M., Volkova T.D., Titova M.A., Gershovich Iu.G., Medvinskaia N.I., Samokhin A.N., Kamynina A.V., Shalgunov V.S., Koroev D.O., Filatova M.P., Oboznaia M.B., Bobkova N.V. (2008). New approaches to the immunotherapy of Alzheimer's disease with the synthetic fragments of alpha 7 subunit of the acetylcholine receptor. Russ. J. Bioorgan. Chem. 34, 43–48 [+]

    The effect of immunization with the synthetic fragments of the alpha 7 subunit of the acetylcholine nicotine receptor on the spatial memory of mice subjected to olfactory bulbectomy, which causes the development of the neurodegenerative disease of Alzheimer’s type, was studied. It was shown that 20% of bulbectomized mice immunized with protein conjugate of 1—23 fragment exhibited good spatial memory. Immunization with the conjugate of peptide construct (159—167)-(179—188) induced good spatial memory in 50% of bulbectomized mice. Thus, the development of immunotherapy with peptide (159—167)-(179—188) seems to be a promising approach to prophylaxis and treatment of Alzheimer’s disease.

    ID:115
  14. Oboznaya M.B., Gilch S., Titova M.A., Koroev D.O., Volkova T.D., Volpina O.M., Schätzl H.M. (2007). Antibodies to a nonconjugated prion protein peptide 95-123 interfere with PrP( Sc ) propagation in prion-infected cells. Cell. Mol. Neurobiol. 27 (3), 271–84 [+]

    We investigated the ability of five peptides corresponding to three different regions of the bovine prion protein (PrP) to elicit antibodies interfering with PrPSc propagation in prion-infected cells.

     

    All peptides induced in rabbits anti-peptide antibodies, most of them reacting with recombinant PrP. Moreover, addition of the serum specific to peptide 95—123 led to a transient reduction of PrPSc levels in persistently prion-infected cells.

    ID:114
  15. Volpina O.M., Volkova T.D., Koroev D.O., Ivanov V.T., Ozherelkov S.V., Khoretonenko M.V., Vorovitch M.F., Stephenson J.R., Timofeev A.V. (2005). A synthetic peptide based on the NS1 non-structural protein of tick-borne encephalitis virus induces a protective immune response against fatal encephalitis in an experimental animal model. Virus Res. 112 (1-2), 95–9 [+]

    Synthetic peptide corresponds to amino acids 37—55 of NS1 non-structural protein from tick-borne encephalitis virus (strain Sophyin) was able to protect 60% of animals against lethal challenge with the homologous highly pathogenic tick-borne encephalitis virus strain, and adoptive transfer experiments indicated the involvement of the antibodies induced by this peptide in its protective activity in mice.

    ID:113
  16. Volpina O.M., Surovoy A.Y., Zhmak M.N., Kuprianova M.A., Koroev D.O., Chepurkin A.V., Toloknov A.S., Ivanov V.T. (1999). A peptide construct containing B-cell and T-cell epitopes from the foot-and-mouth disease viral VP1 protein induces efficient antiviral protection. Vaccine 17 (6), 577–84 [+]

    A new peptide construct Palm135-158-GGA-170-188(Acm) contains a virus specific T-helper epitope within the 170—188 sequence of VP1, in addition to the main antigenic 135—158 region of the foot-and-mouth disease viral VP1 protein (strain A22). The construct has higher protective, antigenic, immunogenic and T-cell proliferative activity then the previously described shorter peptide Palm(2)135—159.

    ID:112
  17. Volpina O.M., Yarov A.V., Zhmak M.N., Kuprianova M.A., Chepurkin A.V., Toloknov A.S., Ivanov V.T. (1996). Synthetic vaccine against foot-and-mouth disease based on a palmitoyl derivative of the VP1 protein 135-159 fragment of the A22 virus strain. Vaccine 14 (14), 1375–80 [+]

    The peptide Palm2 135—159, a dipalmitoyl derivative of the 135—159 fragment of VP1 protein of the foot-and-mouth disease virus strain A22 was synthesized. In the experiments on mice, guinea pigs and sheep Palm2 135—159 possesses antiviral activity. It was shown that the synthetic vaccine provides 1 year protection of sheep against foot-and-mouth disease after a single administration. The peptide vaccine is allowed for veterinary use in Russia.

    ID:111

Olga Volpina

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. 33, office. 234
  • Phone: +7(495)336-57-77
  • E-mail: volpina@ibch.ru

Synthetic fragment of receptor for advanced glycation end products prevents memory loss and protects brain neurons in animals with experimentally induced Alzheimer’s disease. (2017-12-15)

It was established the relationship between ability of synthetic fragments of receptor for advanced glycation end products administrated intranasally as well as immunized to prevent memory loss in animals with experimentally induced Alzheimer’s disease and to prevent neuronal death and to decreased the amyloid-beta level in the brain. Using fluorescent labeled peptide, we revealed its penetration in the brain of mice and colocalization of peptide with amiloyd-beta  plaques. It was shown that amyloid-beta can be one of the molecular target of active peptide. These findings provide a new approach for design of anti-Alzheimer’s disease therapy.

Publications

  1. Volpina O.M., Samokhin A.N., Koroev D.O., Nesterova I.V., Volkova T.D., Medvinskaya N.I., Nekrasov P.V., Tatarnikova O.G., Kamynina A.V., Balasanyants S.M., Voronina T.A., Kulikov A.M., Bobkova N.V. (2018). Synthetic fragment of receptor for advanced glycation end products prevents memory loss and protects brain neurons in olfactory bulbectomized mice. JAD 61 (3), [+]

    Activation of receptor for advanced glycation end products (RAGE) plays an essential role in the development of Alzheimer’s disease (AD). It is known that the soluble isoform of the receptor binds to ligands and prevents negative effects of the receptor activation. We proposed that peptide fragments from RAGE prevent negative effects of the receptor activation during AD neurodegeneration. We have synthesized peptide fragments from surface-exposed regions of RAGE. Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice, which developed some characteristics similar to AD neurodegeneration. We have found that only insertion of fragment (60-76) prevents the memory of OBX mice. Immunization of OBX mice with peptides showed that again only (60-76) peptide protected the memory of animals. Both intranasal insertion and immunization decreased the amyloid-β (Aβ) level in the brain. Activity of shortened fragments of (60-76) peptide was tested and showed only the (60-70) peptide is responsible for manifestation of activity. Intranasal administration of (60-76) peptide shows most protective effect on morpho-functional characteristics of neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we revealed its penetration in the brain of OBX mice as well as colocalization of Flu-labeled peptide with Aβ in the brain regions in transgenic mice. Flu-(60-76) peptide complex with trimer of Aβ was detected by SDS-PAGE. These data indicate that Aβ can be one of the molecular target of (60-70) peptide. These findings provide a new peptide molecule for design of anti-AD drug and for investigation of RAGE activation ways in progression of AD neurodegeneration.

    ID:1949
  2. Koroev D.O., Volpina O.M., Volkova T.D., Kamynina A.V., Filatova M.P., Balasanyants S.M., Samokhin A.N., Bobkova N.V. (2017). A synthetic fragment 60–70 of the receptor for advanced glycation end products exhibits a therapeutic effect in an animal model of Alzheimer’s disease. Russ. J. Bioorgan. Chem. 43 (42), 150–154 [+]

    Six synthetic peptides overlapping a fragment 60-76 of the receptor for advanced glycation end products (RAGE) were studied on a protective effect on spatial memory of animals in the experimental model of Alzheimer's disease. It was shown that only a peptide corresponding to the fragment 60-70 of RAGE exhibits a therapeutic activity. Intranasal administration of this peptide into bulbectomized mice, which develop neurodegenerative features of the Alzheimer type, completely protects animal memory. Thus, it was found that the N-terminal region (60-70) within the peptide sequence 60-76 of RAGE is responsible for the revealed protective effect. The synthetic peptide RAGE-(60-70) could be the basis for the development of a new drug for the treatment of Alzheimer's disease.

    ID:1948