Effects of alpha‐synuclein post‐translational modifications on metal binding

Parkinson’s disease is the second most common neurodegenerative disorder worldwide. Neurodegeneration in this pathology is characterized by the loss of dopaminergic neurons in the substantia nigra, coupled with cytoplasmic inclusions known as Lewy bodies containing α‐synuclein. The brain is an organ...

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Bibliographic Details
Published in:Journal of neurochemistry 2019-09, Vol.150 (5), p.507-521
Main Authors: González, Nazareno, Arcos‐López, Trinidad, König, Annekatrin, Quintanar, Liliana, Menacho Márquez, Mauricio, Outeiro, Tiago F., Fernández, Claudio O.
Format: Article
Language:English
Subjects:
Acetylation
Agglomeration
alpha-Synuclein - chemistry
alpha-Synuclein - metabolism
Binding Sites
Brain
Brain - metabolism
Cations, Divalent - metabolism
Dopamine receptors
Homeostasis
Humans
Inclusion bodies
Inclusions
Lewy bodies
Metal ions
Metals - metabolism
Modulators
Movement disorders
Neurodegeneration
Neurodegenerative diseases
Neurological diseases
Neuromodulation
neurons
Oxidative Stress
Oxygen - metabolism
Parkinson disease
Parkinson Disease - metabolism
Parkinson's disease
Pathology
Phosphorylation
Physiology
post‐translational modification
Protein Aggregation, Pathological
Protein Binding
Protein Domains
Protein interaction
Protein Processing, Post-Translational
protein structure
Proteins
Structure-Activity Relationship
Structure-function relationships
Substantia nigra
Sumoylation
Synuclein
Translation
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Summary:Parkinson’s disease is the second most common neurodegenerative disorder worldwide. Neurodegeneration in this pathology is characterized by the loss of dopaminergic neurons in the substantia nigra, coupled with cytoplasmic inclusions known as Lewy bodies containing α‐synuclein. The brain is an organ that concentrates metal ions, and there is emerging evidence that a break‐down in metal homeostasis may be a critical factor in a variety of neurodegenerative diseases. α‐synuclein has emerged as an important metal‐binding protein in the brain, whereas these interactions play an important role in its aggregation and might represent a link between protein aggregation, oxidative damage, and neuronal cell loss. Additionally, α‐synuclein undergoes several post‐translational modifications that regulate its structure and physiological function, and may be linked to the aggregation and/or oligomer formation. This review is focused on the interaction of this protein with physiologically relevant metal ions, highlighting the cases where metal‐AS interactions profile as key modulators for its structural, aggregation, and membrane‐binding properties. The impact of α‐synuclein phosphorylation and N‐terminal acetylation in the metal‐binding properties of the protein are also discussed, underscoring a potential interplay between PTMs and metal ion binding in regulating α‐synuclein physiological functions and its role in pathology. This article is part of the Special Issue “Synuclein”. This review is focused on the interaction of α‐synuclein with physiologically relevant metal ions, highlighting the cases where metal‐α‐synuclein interactions profile are key modulators of α‐synuclein structural, aggregation, and membrane‐binding properties. The impact of α‐synuclein phosphorylation, sumoylation, and N‐terminal acetylation in the metal‐binding properties of the protein are also discussed, underscoring a potential interplay between post‐translational modifications and metal ion binding in regulating α‐synuclein physiological functions and its role in pathology. This article is part of the Special Issue “Synuclein”.
ISSN:0022-3042
1471-4159
DOI:10.1111/jnc.14721