Neurodegeneration and Neuroprotection
Uğur Tüfekci, PhD Student
Begüm Alural, PhD Student
Erden Eren, PhD Student
Kamer Burak İşçi, MSc Student
Burak İbrahim Arıöz, MSc Student
Bora Taştan, MSc Student
Tuğba Şan, MSc Student
İrem Nur Gökbayrak, MSc Student
Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration of nerve cells. The primary research focus of our group is the molecular mechanism of neurodegeneration and neuroprotection. Through identification of the molecular mechanisms underlying neurodegeneration, we are trying to develop new strategies towards neuroprotection. On the other hand, we are trying to develop novel therapeutic agents for the treatment of neurodegenerative disorders. Our other aim is to identify potential diagnostic/prognostic biomarkers, especially for Alzheimer’s disease. We also focus on the role of miRNAs in the biological and pathological process of the central nervous system.
Our groups investigate the molecular mechanisms that underlie cell death in neurodegeneration and neuroinflammation and assess novel strategies for neuroprotection. Erythropoietin, Lithium and anti-oxidant molecules (Sulforaphane, Resveratrol, Melatonin) will be used future research. We will also search anti-inflammatory effects of these molecules. In a currently funded project, we are looking the resveratrol effect on inflammasome activation in microglial cells. Inflammasome activation is one of the immune responses in innate immunity and it differs from classical immune responses. Both membrane-bound and cytosolic receptors contribute to this process. Besides microbes or microbial molecules, it has been known that metabolic stress products (uric acid crystals, ATP, etc.) and exogenous agents such as asbestos, silica can also trigger inflammasome activation. Inflammasome activation leads to activation of caspase-1, interleukin -1β (IL-1β) and interleukin -18 (IL-18) cytokine release from cells and inflammasome activation may also lead to pyroptotic cell death in the cell. For this reason, inflammasome activation should be prevented under such conditions. Alzheimer’s disease (AD) represents the most common form of dementia. According to World Health Organization (WHO)’s report in 2012, more than 35 million individuals are affected by AD. Currently, there is no cure or any method that would prevent disease progression. The definitive diagnosis of AD can be made only in the postmortem period by examining the brain tissue during a biopsy. Screening of AD patients remains an expensive approach, and it is crucial that ongoing research in this field is focused on developing inexpensive and reliable methods towards early diagnosis of AD. We especially are searching miRNAs expression profile as a biomarker. MicroRNAs (miRNAs) are small, non-coding RNA molecules, which regulate various metabolic activities. Circulating miRNAs are promising candidates for blood-based biomarkers, given their high stability in circulation, tissue- and/or cell-specific expression and ease of miRNA analysis with existing methods (e.g. real-time PCR). Circulating serum miRNAs would be a good choice as biomarkers for neurological and psychiatric disorders. We are preparing a research proposal for miRNA expression profile as a biomarker in Alzheimer’s disease.
Alzheimer’s Disease (AD) and Parkinson’s disease are the most common neurodegenerative diseases. Definitive diagnosis can only be established by pathological evaluation in post-mortem period. Therefore, there is a biomarker need for both definitive diagnosis and development of clinical observation. In recent studies, we developed standard operating procedures (SOPs) for pre-analytical and analytical procedures. We analyzed the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of alpha-synuclein in CSF. miRNAs have a major role in the biological and pathological process of the central nervous system. Apart from biomarker studies, we showed novel effects of two neuroprotective molecules. MicroRNA-451 and 888-5p mediate neuroprotective effects of Erythropoietin and neuroprotective effects of Lithium depends on miR-34a inhibition. In next future, miRNAs expression alternation could be a new therapeutic strategy for neurodegenerative disorders.
|AWARDS AND RECOGNITION
• Eczacıbaşı Medical Incentive Award-2011
• TUBITAK Incentive Award in Medicine- 2008
• Young Scientist Awards from Turkish Academy of Sciences-2006
• L’Oréal & Unesco Turkey National Women in Science Award-2003
Full list and citations: Google Scholar: Sermin Genc
|• Kruse N, Persson S, Alcolea D, Bahl JM, Baldeiras I, Capello E, Chiasserini D, Bocchio Chiavetto L, Emersic A, Engelborghs S, Eren E, Fladby T, Frisoni G, García-Ayllón MS, Genc S, Gkatzima O, Heegaard NH, Janeiro AM, Kováčech B, Kuiperij HB, Leitão MJ, Lleó A, Martins M, Matos M, Mollergard HM, Nobili F, Öhrfelt A, Parnetti L, de Oliveira CR, Rot U, Sáez-Valero J, Struyfs H, Tanassi JT, Taylor P, Tsolaki M, Vanmechelen E, Verbeek MM, Zilka N, Blennow K, Zetterberg H, Mollenhauer B. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study. Neurobiol Aging. 2015 Sep;36(9):2587-96.
• Alural B, Ayyildiz ZO, Tufekci KU, Genc S, Genc K. Erythropoietin Promotes Glioblastoma via miR-451 Suppression. Vitam Horm. 2017;105:249-271. doi: 10.1016/bs.vh.2017.03.002. Epub 2017 Apr 19. PubMed PMID: 28629521.
• van Waalwijk van Doorn LJ, Gispert JD, Kuiperij HB, Claassen JA, Arighi A, Baldeiras I, Blennow K, Bozzali M, Castelo-Branco M, Cavedo E, Emek-Savaş DD, Eren E, Eusebi P, Farotti L, Fenoglio C, Ormaechea JF, Freund-Levi Y, Frisoni GB, Galimberti D, Genc S, Greco V, Hampel H, Herukka SK, Liu Y, Lladó A, Lleó A, Nobili FM, Oguz KK, Parnetti L, Pereira J, Picco A, Pikkarainen M, de Oliveira CR, Saka E, Salvadori N, Sanchez-Valle R, Santana I, Scarpini E, Scheltens P, Soininen H, Tarducci R, Teunissen C, Tsolaki M, Urbani A, Vilaplana E, Visser PJ, Wallin AK, Yener G, Molinuevo JL, Meulenbroek O, Verbeek MM. Improved
Cerebrospinal Fluid-Based Discrimination between Alzheimer’s Disease Patients and Controls after Correction for Ventricular Volumes. J Alzheimers Dis. 2017;56(2):543-555. doi: 10.3233/JAD-160668. PubMed PMID: 28059783.
• Alural B, Genc S, Haggarty SJ. Diagnostic and therapeutic potential of microRNAs in neuropsychiatric disorders: Past, present, and future. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Feb 6;73:87-103. doi: 10.1016/j.pnpbp.2016.03.010. Epub 2016 Apr 9. PubMed PMID: 27072377; PubMed Central PMCID: PMC5292013.
• Alural B, Ozerdem A, Allmer J, Genc K, Genc S. Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells. Front Cell Neurosci. 2015 May 28;9:209.
• Alural B, Duran GA, Tufekci KU, Allmer J, Onkal Z, Tunali D, Genc K, Genc S. EPO Mediates Neurotrophic, Neuroprotective, Anti-Oxidant, and Anti-Apoptotic Effects via Downregulation of miR-451 and
miR-885-5p in SH-SY5Y Neuron-Like Cells. Front Immunol. 2014 Sep 30;5:475.
• Yiş U, Tüfekçi UK, Genç Ş, Çarman KB, Bayram E, Topçu Y, Kurul SH. Expression patterns of micro-RNAs 146a, 181a, and 155 in subacute sclerosing panencephalitis. J Child Neurol. 2015 Jan;30(1):69-74.
• Cavdar Z, Egrilmez MY, Altun ZS, Arslan N, Yener N, Sayin O, Genc S, Genc K, Islekel H, Oktay G, Akdogan GG. Resveratrol reduces matrix metalloproteinase-2 activity induced by oxygen-glucose deprivation and reoxygenation in human cerebral microvascular endothelial cells. Int J Vitam Nutr Res. 2012 Aug;82(4):267-74.
• Lee SE, Tartaglia MC, Yener G, Genç S, Seeley WW, Sanchez-Juan P, Moreno F, Mendez MF, Klein E, Rademakers R, López de Munain A, Combarros O, Kramer JH, Kenet RO, Boxer AL, Geschwind MD, Gorno-Tempini ML, Karydas AM, Rabinovici GD, Coppola G, Geschwind DH, Miller BL. Neurodegenerative disease phenotypes in carriers of MAPT p.A152T, a risk factor for frontotemporal dementia spectrum disorders and Alzheimer disease. Alzheimer Dis Assoc Disord. 2013 Oct-Dec;27(4):302-9.
• Genc K, Egrilmez MY, Genc S. Erythropoietin induces nuclear translocation of Nrf2 and heme oxygenase-1 expression in SHSY5Y cells. Cell Biochem Funct. 2010 Apr;28(3):197-201.
|• Tüfekci KU, Oner MG, Meuwissen RL, Genç S. The role of microRNAs in human Diseases in miRNomics: MicroRNA Biology and Computational Analysis. 2014, Springer. Editors: Malik Yousef, Jens Allmer. ISBN: 978-1-62703-748-8.
• Tüfekci KU, Meuwissen RL, Genç S. The role of microRNAs in biological processes in miRNomics: MicroRNA Biology and Computational Analysis. 2014, Springer. Editors: Malik Yousef, Jens Allmer. ISBN: 978-1-62703-748-8