Genc Lab.

Genc Lab.

Neurodegeneration and Neuroprotection

OVERVIEW

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.

RESEARCH INTERESTS

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.

Şermin Genç Şekil   RESEARCH HIGHLIGHTS

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.