{"title":"Alpha-Synuclein Aggregation, Cholesterol Transport, and the 18-kDa Translocator Protein","authors":"J. Dimitrova‐Shumkovska, Ljupcho Krstanoski","doi":"10.5772/intechopen.83459","DOIUrl":"https://doi.org/10.5772/intechopen.83459","url":null,"abstract":"The molecular responses to counteract diseases, including insulting conditions such as injury and pathogen infection, involve coordinated modulation of gene expression programs. The association of alpha synuclein ( α -Syn) with several progressive disorders has focused the research on its induced conformational behavior as critical for uncovering the “secrets” for progression of α -synucleinopathies. Cholesterol is one of the lipid components crucial for regular proliferation of the nervous tissue. Its interaction with α -Syn may offer other insights to α -Syn normal expression. Discovering that the molecular regulatory mechanisms responsible for prevention of α -Syn aggregation may be manifested through microRNA (miRNA) regulated gene expression is also crucial for widening the perception of neuropathology. The 18-kDa translocator protein (TSPO) localized on the outer mitochondrial membrane is able to regulate various cellular and tissue functions, with key role as cholesterol transporter for neurosteroid synthesis. TSPO up-regulation, has been connected to several diseases, including cancer, neuronal damage, and inflammation. Connection may also be established between TSPO expression and fatty acid oxidation, thus unveiling new possibilities in the research of α -Syn overexpression. However, expression of TSPO in the neuroinflammatory environment is probably the best starting point for targeting TSPO as a suitable therapeutic target.","PeriodicalId":190977,"journal":{"name":"Synucleins - Biochemistry and Role in Diseases","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134497039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheeza Khan, Zeba Mueed, R. Deval, P. Rai, D. Prajapati, N. Poddar
{"title":"Role of Osmolytes in Amyloidosis","authors":"Sheeza Khan, Zeba Mueed, R. Deval, P. Rai, D. Prajapati, N. Poddar","doi":"10.5772/INTECHOPEN.83647","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.83647","url":null,"abstract":"Osmolytes are naturally occurring small organic molecules present in all kingdoms of life. These organic molecules are accumulated by living systems to cir-cumvent stress conditions. A number of human diseases have been grouped under the protein-misfolding diseases. These entire diseases share the same hallmarks of the presence of cellular inclusions and plaques that are deposited in the cells and tissues affected by the disease. These misfolded forms of protein are responsible for initiating toxic cascades in the cell, causing vesicle dystrafficking, synaptic and cell organelle dysfunction, and ultimately cell death. Published results suggest that cells regulate many biological processes such as protein folding, protein disaggregation, and protein-protein interactions via accumulation of specific osmolytes. Since, as of now, complete cure for these protein-misfolding disorders does not exist; there-fore, it becomes increasingly important to review the recent works on this aspect to develop strategies for therapeutics. It has been shown that certain osmolytes can prevent the proteins from misfolding. Thus, osmolytes can be utilized as therapeutics for such diseases. In this review article, we discuss the role of naturally occurring osmolytes in various forms of amyloidosis associated with human diseases.","PeriodicalId":190977,"journal":{"name":"Synucleins - Biochemistry and Role in Diseases","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127054965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic Potential of Baicalein in Parkinson’s Disease: Focus on Inhibition of α-Synuclein Oligomerization and Aggregation","authors":"Hayate Javed, S. Ojha","doi":"10.5772/INTECHOPEN.83589","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.83589","url":null,"abstract":"Parkinson’s disease (PD) is the most common neurodegenerative diseases, which affects the people in old age. The neuropathological symptoms of PD include the degeneration of dopaminergic neurons in the substantia nigra pars compacta, and presence of intracellular inclusions of α -synuclein ( α -syn) aggregates. α -Syn, a natively unfolded protein, has been found to play a key role in PD pathology. Several mechanistic studies revealed the numerous aspects of α -syn fibrillation and aggregation process that lead to dopaminergic neurodegeneration in PD. Till to date, there is no complete cure of PD, but some therapeutic agents are able to halt the disease progression. Scutellaria baicalensis Georgi is a traditional Chinese medicine commonly used to treat the central nervous system diseases. Recently, it has been confirmed that root of S. baicalensis Georgi contains baicalein (5,6,7-trihy-droxyflavone) as a major bioactive flavone constituent. Baicalein possess numerous pharmacological properties such as antiaggregation of amyloid proteins including α -syn, antioxidant, anti-inflammatory, and antiapoptotic. In the light of these properties, baicalein has potential therapeutic efficacy for PD. In this chapter, we explored the pharmacological protective actions of baicalein against α -syn fibrillation and aggregation that make it suitable for PD treatment and also discussed the possible mechanisms underlying the effects.","PeriodicalId":190977,"journal":{"name":"Synucleins - Biochemistry and Role in Diseases","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123210492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Introductory Chapter: Little Pigeons Can Carry Great Messages","authors":"A. Surguchov","doi":"10.5772/INTECHOPEN.82670","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.82670","url":null,"abstract":"","PeriodicalId":190977,"journal":{"name":"Synucleins - Biochemistry and Role in Diseases","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115384458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease","authors":"Nevra Alkanli, A. Ay","doi":"10.5772/INTECHOPEN.82808","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.82808","url":null,"abstract":"Parkinson’s disease (PD) is a neurodegenerative disorder affecting the motor system and occurring in the central nervous system. One of the symptoms of PD is accumulation of Lewy bodies and Lewy neurites. The alpha-synuclein (SNCA) gene is part of the protein complex called Lewy body. The SNCA gene encoding a presynaptic protein product is thought to play a role in PD-related important pathways. It is suggested that there is a relationship between the risk of PD development and SNCA levels, and it is suggested that SNCA level is an important marker in PD diagnosis. Various polymorphisms have been identified in the 5 ′ and/or 3 ′ UTR regions of the SNCA gene, and as a result of these polymorphisms, changes occur in the binding of transcription factors. The identification of the roles of SNCA gene polymorphisms in PD development may enable the development of new methods for the treatment of PD.","PeriodicalId":190977,"journal":{"name":"Synucleins - Biochemistry and Role in Diseases","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127109030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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