Browsing by Subject "Neurodegenerative diseases"
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Item Open Access Bioactive nanomaterials for neural engineering(Springer, Cham, 2016) Sever, Melike; Uyan, İdil; Tekinay, Ayse B.; Güler, Mustafa O.; Zhang, L. G.; Kaplan, D. L.Nervous system is a highly complex interconnected network and higher organisms including humans have limited neural regeneration capacity. Neurodegenerative diseases result in significant cognitive, sensory, or motor impairments. Following an injury in the neural network, there is a balance between promotion and inhibition of regeneration and this balance is shifted to different directions in central nervous system (CNS) and peripheral nervous system (PNS). More regeneration capacity is observed in the PNS compared to the CNS. Although, several mechanisms play roles in the inhibitory and growth-promoting natures of the CNS and PNS, extracellular matrix (ECM) elements are key players in this process. ECM is a three-dimensional environment where the cells migrate, proliferate, and differentiate (Rutka et al. 1988; Pan et al. 1997). After a comprehensive investigation of the interactions between the ECM proteins and cell receptors, the ECM environment was found to regulate significant cellular processes such as survival, proliferation, differentiation, and migration (Yurchenco and Cheng 1994; Aszodi et al. 2006). Its components have major roles not only in neurogenesis during development of the nervous system but also in normal neural functioning during adulthood (Hubert et al. 2009).Item Open Access Mammalian target of rapamycin (mTOR), aging, neuroscience, and their association with aging-related diseases(Elsevier Inc., 2016) Celebi-Birand, Ergül Dilan; Karoğlu, Elif Tuğçe; Doldur-Ballı, Füsun; Adams, Michelle M.; Maiese, K.Normal aging is accompanied by cognitive impairment with subtle cellular and molecular changes in the brain, whereas, pathological brain aging manifests as severe behavioral impairments with cellular pathology. Understanding the factors that contribute to both states is undoubtedly important for determining appropriate interventions that alter their progression. Mammalian target of rapamycin (mTOR) signaling has been implicated in affecting lifespan and age-related diseases such as cancer. The relationship of mTOR signaling with pathological brain aging has been more extensively studied, whereas the association with normal brain aging is not well understood. In this chapter we present information about normal and pathological brain aging, the relationship with mTOR signaling and use information from other age-related diseases to suggest that mTOR may have a role in promoting the cellular and molecular changes that underlie age-related cognitive changes. Future work should be directed towards understanding the precise role of mTOR signaling in brain aging. © 2016 Elsevier Inc. All rights reserved.Item Open Access Peptide based ligand discovery to prevent protein aggregation in neurodegenerative disease conditions(Bilkent University, 2019-09) Beğli, ÖzgeNeurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are cognitively and physically debilitating and progressive diseases due to the gradual and irreversible loss of discrete neuronal populations in the brain. In addition to millions of people worldwide suffering from them, the prevalence of the neurodegenerative diseases dramatically increases with the increasing lifespan of the population. Most of the current therapeutic strategies either target toxic aggregates in neurons or support the healthy cells in diseased region. However, these interventions provide only symptomatic relief and deceleration of disease progression. Besides, aggregation involves a locking phase in which irreversible transition of soluble monomeric and oligomeric molecules into insoluble fibrous structures occurs. During aggregation, fragmentation of mature fibrils leads to the formation of new oligomeric structures possessing seeding activity. The seeds behaving as a nucleation unit trigger other structures to join the accumulated proteins. Synthetic biology is an emerging field that suggests therapeutic solutions for several diseases. Development of synthetic proteins such as artificial transcription factors and improved antibodies, artificial cell transplants with controlled secretion, designed inhibitory RNA molecules and antisense oligonucleotides, gene circuits and logic gates, synthetic viruses as an advanced delivery system and genome editing technologies using programmable nucleases are revolutionary approaches for the diagnosis and treatment of diseases. With the utilization of a variety of advanced tools, synthetic biology is extremely promising to treat neurodegenerative disorders too. In this study, biotechnological approaches and tools such as gene cloning, yeast surface display and phage display library have been used to target neurodegenerative proteins before aggregation takes place. Neurodegenerative proteins were cloned into a plasmid DNA within bacteria and displayed on the surface of Saccharomyces cerevisiae cells. A phage display library has been screened against those neurodegenerative proteins and binding peptides of these proteins have been selected following recursive rounds of binding and washing steps. Peptides that bind to neurodegenerative proteins with high affinity possess the potential to block them and prevent the initiation of aggregation. Beside to the promising results of neuroprotective and neurorestorative interventions, this strategy can provide prevention of aggregation which is the underlying cause of neurodegeneration.