NDLI: α-Synuclein Misfolding Versus Aggregation Relevance to Parkinson’s Disease: Critical Assessment and Modeling

Content Provider	Springer Nature Link
Author	Berrocal, Ruben Vasquez, Velmarini KRS, Sambasiva Rao Gadad, Bharathi S KS, Rao
Copyright Year	2014
Abstract	α-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in Parkinson’s disease (PD). The aggregation of α-synuclein is believed to be a critical event in the disease process. α-Synuclein is characterized by a remarkable conformational plasticity, adopting different conformations depending on the environment. Therefore, it is classified as an “intrinsically disordered protein.” Recently, a debate has challenged the view on the intrinsically disordered behavior of α-synuclein in the cell. It has been proposed that α-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why α-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in α-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed bioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson’s disease.
Starting Page	1417
Ending Page	1431
Page Count	15
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	51
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2014-08-20
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	α-Synuclein Aggregation Parkinson’s disease Misfolding Conformation Metals Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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