Genetic Variants in SNCA and the Risk of Sporadic Parkinson’s Disease and Clinical Outcomes: A Review

Campêlo, Clarissa Loureiro das Chagas; Silva, Regina H.

doi:10.1155/2017/4318416

Cited by 42 publications

(44 citation statements)

References 105 publications

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“…In Lewy bodies, SNCA protein is predominant and is therefore known to be associated with the etiology of PD. SNCA also has an important function in the pathological process of PD [26,27]. SNCA, an important component of Lewy bodies, is one of the distinctive features of PD [28][29][30].…”

Section: Protein Encoded By Snca Genementioning

confidence: 99%

“…Several genes and several polymorphisms of the SNCA gene have been identified in GWAS. It has been determined that some of these gene polymorphisms may be important risk factors especially for sporadic PD [26]. Polymorphisms in different regions of the SNCA gene have been studied in various studies with different populations [7].…”

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

“…In a study conducted with the Korean population, it was determined that the G allele of rs356219 gene polymorphism was associated with the risk of PD development [44]. In studies conducted with populations of North America, Spain, Russia, and China, rs356219 gene polymorphism was identified as a genetic risk factor for PD development risk [26].…”

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

“…In the SNCA promoter (SNCA-Rep 1), it was determined that the localized Rep 1 and 3′ untranslated region polymorphisms interfered with the transcription binding regions and played an important role in increasing PD susceptibility. Thus, target regions of miRNAs that alter SNCA gene expression are formed or disappear [26]. The significant difference was determined between Rep 1-259 allele and low levels of SNCA mRNA in postmortem brain tissues of patients with PD.…”

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

See 3 more Smart Citations

The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease

Alkanlı¹,

Ay²

2020

Synucleins - Biochemistry and Role in Diseases

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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.

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Section: Protein Encoded By Snca Genementioning

confidence: 99%

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

Section: Gene Polymorphisms Of Sncamentioning

confidence: 99%

See 2 more Smart Citations

The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease

Alkanlı¹,

Ay²

2020

Synucleins - Biochemistry and Role in Diseases

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“…We investigated the functions of the identified interacting proteins with the highest influence scores (APOE, CASP6, GSK3B, RNF19A, MAPT, and CSNK2A2). The PPI network included several central nodes (TAF1, PARK7, SNCA, PARK2, UCHL1, MAPT, HTPR2, and NR4A2) involved in Parkinson's disease (Campelo and Silva, 2017;Domingo, et al, 2016;Rocha, et al, 2018), as well as others (UBB, LRRK2, APP, GSK3B, FYN, SEPT4, RANBP2, ABL1, and MAP1LC3B).…”

Section: Parkinson's Disease Associated Network Analysismentioning

confidence: 99%

Disease associated protein-protein interaction network reconstruction based on comprehensive influence analysis

Zhu

Ling

et al. 2019

Preprint

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Proteins and their interactions are fundamental to biological system. With the scientific paradigm shifting to systems biology, functional study of proteins from a network viewpoint to get a deep understanding of their roles in human life and diseases being increasingly essential. Although several methods already existed for protein-protein interaction (PPI) network building, the precise reconstruction of disease associated PPI network remains a challenge. In this paper we introduce a novel concept of comprehensive influence of proteins in network, in which direct and indirect connections are adopted for the calculation of influential effects of a protein with different weights. With the optimized weights, we calculate and select the important proteins and their interactions to reconstruct the PPI network for further validation and confirmation. To evaluate the performance of the method, we compared our model with the six existed ones by using five standard data sets. The results indicated that our method outperforms the existed ones. We then applied our model to prostate cancer and Parkinson's disease to predict novel disease associated proteins for the future experimental validation. Author SummaryThe diverse protein-protein interaction networks have dramatic effects on biological system. The disease associated PPI networks are generally reconstructed from experimental data with computational models but with limited accuracy. We developed a novel concept of comprehensive influence of proteins in network for reconstructing the PPI network. Our model outperforms the state-of-the-art ones and we then applied our model to identify novel interactions for further validation. / 21experimental methods and the complexity of biomedical systems, the experimental results often present high false-positive and false-negative rates (Cheng, et al., 2016). Moreover, experimental verification of the PPI network is time consuming and expensive. Therefore, rapid and accurate computational methods represent useful alternative for predicting protein interactions, with such results providing guidance for experiments, including determination of unknown relationships between disease-causing genes and protein interactions (Zhu, et al., 2015). Such knowledge can be useful to the understanding of protein structure and evolution, as well as the overall function of the network and its associated dynamic processes (Cowen, et al., 2017;Hoeng, et al., 2014).The unknown interaction between proteins can be predicted by the theory of complex network. PPI network consists of nodes and edges, with the nodes representing proteins and the edges representing associations or interactions between the two proteins (Gani, et al., 2015). Libennowell et al. considered the influence of common neighbor nodes in the network and introduced similarity indices to include common neighbors (Libennowell and Kleinberg, 2007). Pujari et al. suggested that each attribute of a pair of connected proteins represents different information (Pujari and Kanawati, 2012), and L...

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Auditory Dysfunction in Parkinson's Disease

2020

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A BS TRACT: PD is a progressive and complex neurological disorder with heterogeneous symptomatology. PD is characterized by classical motor features of parkinsonism and nonmotor symptoms and involves extensive regions of the nervous system, various neurotransmitters, and protein aggregates. Extensive evidence supports auditory dysfunction as an additional nonmotor feature of PD. Studies indicate a broad range of auditory impairments in PD, from the peripheral hearing system to the auditory brainstem and cortical areas. For instance, research demonstrates a higher occurrence of hearing loss in early-onset PD and evidence of abnormal auditory evoked potentials, event-related potentials, and habituation to novel stimuli. Electrophysiological data, such as auditory P3a, also is suggested as a sensitive measure of illness duration and severity. Improvement in auditory responses following dopaminergic therapies also indicates the presence of similar neurotransmitters (i.e., glutamate and dopamine) in the auditory system and basal ganglia. Nonetheless, hearing impairments in PD have received little attention in clinical practice so far. This review summarizes evidence of peripheral and central auditory impairments in PD and provides conclusions and directions for future empirical and clinical research.Among neurological disorders, which are the leading cause of disability in the world, Parkinson's disease (PD) shows the highest growth in prevalence, rate of deaths, and disability-adjusted life-years between 1990 and 2015, and it is estimated to double over the next 20 years. 1 The etiology of PD is often unknown and mostly occurs in sporadic form, possibly arising from the association of genetic and environmental risk factors. 2,3 As a progressive disease, PD is characterized by early major death of dopaminergic neurons in the SNpc within the basal ganglia that leads to classical parkinsonian and secondary motor symptoms. 2,4 PD pathology involves extensive regions of the nervous system, various neurotransmitters (e.g., dopaminergic and nondopaminergic neurotransmitters), and protein aggregations other than just Lewy bodies or Lewy neurites (i.e., abnormal aggregation of insoluble α-synuclein protein [SNCA]) 2 that account for a wide range of clinical symptoms and signs observed in PD. 5 Thus, multiple nonmotor symptoms (NMSs) develop throughout the PD progress, some of which precede the motor dysfunction by more than a decade. 2 For instance, fatigue, neuropsychiatric symptoms, autonomic dysfunction, gastrointestinal symptoms, sensory deficits (e.g., visual impairments, 6 olfactory dysfunction, 7 taste disorders, 8 somatosensory abnormalities, 9 and auditory disorders 10,11 ), and sleep problems are within common NMSs in early PD. 2,3 Among sensory dysfunctions as NMSs of PD, somatic sensations, such as pain and paraesthesias, have received ---

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Genetic Variants in SNCA and the Risk of Sporadic Parkinson’s Disease and Clinical Outcomes: A Review

Cited by 42 publications

References 105 publications

The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease

The Relationship between Alpha-Synuclein (SNCA) Gene Polymorphisms and Development Risk of Parkinson’s Disease

Disease associated protein-protein interaction network reconstruction based on comprehensive influence analysis

Auditory Dysfunction in Parkinson's Disease

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