Description
Neurodegenerative diseases represent an increasing threat to the society and families in both countries. Deposition of toxic proteins in the brain leads to dementia, motor dysfunction, and psychiatric problems.The goal of this project is to develop a new strategy for the treatment of Alzheimer's disease (AD) and enhance research-based knowledge in Latvia through a long-term collaboration with the project partners. Specifically, we will set up a joint programme to investigate whether amino acid changes could be exploited as an innovative method to dissolve higher order Aβ aggregates and to enhance clearance of Aβ from the brain into the blood stream. The research groups at the Organic Synthesis Institute of Latvia (OSI) will provide expertise in structural analyses for an iterative set of experiments. The University of Oslo will provide knowledge and expertise in the field of disease models and analyses, while the University of Latvia will provide access to world-wide unique mouse models, and are skilled in the performance of behavioral and cognitive tests. The project also involves the opportunity of exchange of Latvian students to Norway for in-vivo investigations and methods transfer. The project is expected to result in 4 internationally refereed scientific publications, 4 scientific publications co-authored by one or more reserchers from Norway and Latvia and 4 scientific publications
Summary of project results
The overall goal of this project was to develop the new strategy for the treatment of the Alzheimer’s disease (AD). Researchers from Organic syntheses institute have performed in vitro assays (mainly NMR and Thioflavin T) for interaction studies between hAβ and Aβ fragments, made two constructs based on Aβ(A2V)1-6 with two different cell penetrating peptides tags to assist passage over the blood brain barrier, TAT-Aβ(A2V)1-6 and AntP-Aβ(A2V)1-6. A new method for overexpression of Aβ and variants thereof has also been established where researchers made use of a solubility tag from spider-silk protein. Results obtained during the project have been compiled into one published article, one manuscript and one submitted review article from OSI. Researchers form university of Latvia investigated the short sequence peptides using in vivo models (by implementing behavioural and cognitive methods) and ex vivo methods (immunohistochemical staining and western blotting) in tight collaboration with both other partners: Organic Synthesis Institute of Latvia and University of Oslo. To reveal the positive effects of different mutated amyloid beta peptides, in vivo experiments (surgical implantation of Alzet pumps carrying different amyloid beta peptides) were taking place in the laboratory of the Norwegian partner Prof. Jens Pahnke. Western blot method validation for the assessment of the toxic amyloid beta 42 and 40 in the transgenic mice brain with 6E10 antibody that recognizes both: APP protein (~100 kDa) and amyloid beta 42 and 40 (~4 kDa) has been performed. Research project was performed in synergy with the Scholarship Activity ‘Enhancing human capital and knowledge in health science by institutional cooperation and mobility between the University of Latvia and three Norwegian universities’ No. EEZ/NFI/S/2015/019. 2 PhD students and 1 postdoctoral researcher exchange to the University of Oslo, Department of Neuro-/-Pathology (PAT) Translational Neurodegeneration and Neuropathology Lab) has been done in order to perform project experiments. A novel approach in the area of Alzheimer disease therapy have been developed. The basic research knowledge in the field of health (subfields Structural Chemistry, Histology, Histochemistry, Tissue Culture, General Pathology, Pharmacological Sciences and Psychiatry) is much deeper now and promotes further cooperation. Researchers have constructed a new expression system for over-expression of Aβ, far superior previous published protocols in terms of yields.
Summary of bilateral results
Long-term collaboration will be maintained through the personal collaboration developed during the project and by targeting future funding opportunities for joint research applications under Horizon 2020 and other international programs. One successful collaboration is currently running between Henrik Biverstål and Jens Pahnke (JPND, PROP-AD, funded since Jan 2017). Two projects under the Horizont 2020 sub-program Era Net were submitted by Jens Pahnke and Baiba Jansone ("ERARE TreatNCL" and "ERA Neuron JTC2017 UltraABC"). Sustainability of the achieved results have been and will further be ensured by publication of the generated knowledge in well-established, peer-reviewed journals. The project web pages will be available after the end of the project and will be further developed as platform for the groups. The synergy activity between research project NFI/R/2014/023 "Benefits and detrimental effects of sequence variants of Amyloid-p: towards the use of small peptides for aggregate dissolution therapy in dementia" and Scholarship Activity project Nr. EEZ1NFI1S120l5/019 "Enhancing human capital and knowledge in health science by institutional cooperation and mobility between the University of Latvia and three Norwegian universities" provided with the excellent opportunity to exchange the students (5 Master students and 1 Bachelor student, two PhD students (Jolanta Upīte and Vladimirs Piļipenko) and, as well as perform the academic staff mobility Postdoc Ulrika Beitnere) and Prof. Baiba Jansone to additionally strengthen the collaboration between the universities. Even more, PhD students Jolanta Upīte was continuing her research work at University of Oslo at Prof. Jens Pahnke lab after the ending of this mobility program. On January and February in 2017, she was working on experiments in connection with ongoing research project between universities and her PhD thesis work in Oslo University. Sustainability regarding the students exchange between universities will be maintained in the nearest further, for example, PhD student Jolanta Upīte will continue her research work at Prof. Jens Pahnke lab in autumn 2017.