α-Synuclein: An All-Inclusive Trip Around its Structure, Influencing Factors and Applied Techniques.
in silico studies
intrinsically disordered protein
protein interaction
secondary and tertiary structure
synucleinopathy
Journal
Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
02
2021
accepted:
02
06
2021
entrez:
26
7
2021
pubmed:
27
7
2021
medline:
27
7
2021
Statut:
epublish
Résumé
Alpha-synuclein (αSyn) is a highly expressed and conserved protein, typically found in the presynaptic terminals of neurons. The misfolding and aggregation of αSyn into amyloid fibrils is a pathogenic hallmark of several neurodegenerative diseases called synucleinopathies, such as Parkinson's disease. Since αSyn is an Intrinsically Disordered Protein, the characterization of its structure remains very challenging. Moreover, the mechanisms by which the structural conversion of monomeric αSyn into oligomers and finally into fibrils takes place is still far to be completely understood. Over the years, various studies have provided insights into the possible pathways that αSyn could follow to misfold and acquire oligomeric and fibrillar forms. In addition, it has been observed that αSyn structure can be influenced by different parameters, such as mutations in its sequence, the biological environment (e.g., lipids, endogenous small molecules and proteins), the interaction with exogenous compounds (e.g., drugs, diet components, heavy metals). Herein, we review the structural features of αSyn (wild-type and disease-mutated) that have been elucidated up to present by both experimental and computational techniques in different environmental and biological conditions. We believe that this gathering of current knowledge will further facilitate studies on αSyn, helping the planning of future experiments on the interactions of this protein with targeting molecules especially taking into consideration the environmental conditions.
Identifiants
pubmed: 34307295
doi: 10.3389/fchem.2021.666585
pii: 666585
pmc: PMC8292672
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
666585Informations de copyright
Copyright © 2021 Bisi, Feni, Peqini, Pérez-Peña, Ongeri, Pieraccini and Pellegrino.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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