Pleiotrophin And Midkine As

PLEIOTROPHIN AND MIDKINE AS BIOMARKERS AND POSSIBLE DRUG TARGETS IN DEMENTIAS

Author: Sara Martín Martínez. Scientific Coordinators: Gonzalo Herradón Gil-Gallardo, Marta del Campo Milán. Institution: University CEU-San Pablo (Madrid, Spain).

INTRODUCTION: Pleiotrophin (PTN) and Midkine (MK) constitute a small family of heparin binding factors, with overlapping diverse functions in the maintenance of the central nervous system (CNS). Recent studies highlight the role of these cytokines in the modulation of neuroinflammatory processes on brain damage. Dysregulation of neuroinflammatory mechanisms play a relevant role in the development of different neurodegenerative dementias. specially related to FTD and the development

AIM: In this project we aimed to study the relation between these cytokines and different dementia types (Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Lewy Bodies Dementia (LBD)) through the neuroinflammatory response, using patients’ cerebrospinal fluid (CSF).

MATERIALS AND METHODS: The concentration of PTN, MK and IL-6 was analyzed in CSF from non-demented controls (CON, n = 195), AD (n = 230), FTD (n = 199) and LBD (n = 123) patients using PEA-extension assay (Olink® Proteomics). Correlation of these proteins with the classical AD CSF biomarkers (β-amyloid 1-42 (Aβ142); total concentration of tau (t-Tau) and hyperphosphorylated tau (p-Tau)) and MiniMental State Examination (MMSE) test was also performed.

RESULTS: CSF PTN was decreased in AD patients (p < 0.05) compared to controls and correlated with both t-Tau and p-Tau in AD. CSF MK was decreased in FTD patients compared to controls and AD (p < 0.05) and correlated with Aβ1-42 in LBD patients only and with Tau forms in AD and FTD patients. CSF IL-6 remained similar across the different diagnostic groups. PTN and MK levels inversely correlated in all the subjects, suggesting a possible interconnection between them on the CONCLUSION: Our findings show the possibility that PTN and MK could be involved in specific types of dementias associated to neurodegeneration and neuroinflammation. PTN might be specially related to AD, where might be associated with the development of neurofibrillary tangles (NFTs). MK seems to be

development of dementia. of tau aggregates in this dementia. These data suggest that PTN and MK are involved in the pathophysiology of AD and FTD respectively. Further studies are warranted to analyze their potential as novel targets for the development of therapeutic and/or diagnostic tools.

Questions & answers

Please, tell us a little bit more about yourself. My name is Sara Martín and I am from Madrid, Spain. I am a Graduate in Chemistry specialised in Drug Discovery, and currently I am studying a Master’s Degree in Drug Research and Marketing in Madrid. Since I have started the Bachelor, I have developed a special interest in Organic Chemistry focused on the synthesis of molecules with a therapeutic aim, knowing the chemistry inside the different diseases and how the organism react by the action of drugs. I find this idea it really interesting and complex, specially in Neurodegenerative disorders, in which I would be very pleased to be specialist one day, being part of an investigation group.

Tell us a bit more about your research and its significance. The centre of this research is around a small family of proteins, Pleiotrophin (PTN) and Midkine (MK), proposed as possible new targets for the treatment of neurodegenerative diseases such as Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD) and Lewy Bodies Dementia (LBD). PTN and MK are involved in several organism functions associated with growing and reapairing cells and tissues during embryogenesis, where were highly expressed rather than in adults, which are expressed in specific areas of the brain. Several researchs reported their paper in different Central Nervous System (CNS) diseases such as alcoholism and drug addiction. Furthermore, novel studies show evidences of the implication of PTN and MK in different dementias, as they could participate in several pathways which are associated with the neuroinflammatory response characteristic in dementias. Because of that, in this study we did a statistical study where we analyzed the expression of both proteins in selected patients with different dementias, obtaining certain hypothesis which could be interesting to contrast with further statistical and analytical studies in a way to find a possible innovative therapy for these diseases.

What was the biggest challenge whilst carrying out the research and how did you overcome that? All this project supposed a big challenge to me. Everything was new for me, what I found exciting because it gave me the chance to learn new thecniques, concepts and skills that have enriched me for future projects. Although, the biggest challenge was doing the statistical study, because considering the circimstances we are living nowadays, I have to learn Statistics and manage SPSS to manipulate the data by myself. However, I was really enthuastic with the idea, so I put all my effort to do it, using all the resourses that I have. Finally, here is the result.

In your opinion, what is the benefit of joining ESSP and what advice do you have for students undertaking research in the future? Joining ESSP is an excellent oportunity, for me as a novel researcher, to have a publication and, related to that, to make my work know explaining its significnace. It is a useful way to share your work with the rest of the students interested in science, exploring different ways of investigation that are developing actually, adquiring new ideas and amplying your knowledge. My advice is to not give up. Research is not an easy way to follow, it requieres time and a it suppose a big effort, but it is also satisfying when you see your results. So, if you like science, you feel amused with the project and you have a great team which potenciates that feeling and they could give you all the tools to learn all about it, go ahead, because you will learn a lot from them and for yourself.