Comparing the copper binding features of alpha and beta synucleins

Rodríguez, Esaú E.; Ríos, Anacelia; Trujano-Ortiz, Lidia G.; Villegas, Atenea; Castañeda‐Hernández, Gilberto; Fernández, Claudio O.; González, Felipe J.; Quintanar, Liliana

doi:10.1016/j.jinorgbio.2022.111715

Cited by 2 publications

(2 citation statements)

References 42 publications

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“…Various amyloidogenic peptides and their variants have been intensely investigated for their coordination sites with Cu + or Cu 2+ , but not to an equal extent. Among these peptides, Aβ has been the most extensively examined, followed by αSyn and IAPP [ 11 , 12 , 13 , 14 , 15 ]. On the other hand, tau and other amyloid proteins have a smaller amount of information available regarding their interactions with metal ions [ 16 , 17 , 18 ].…”

Section: Factors Influencing Protein Aggregationmentioning

confidence: 99%

Unveiling the Effects of Copper Ions in the Aggregation of Amyloidogenic Proteins

Oliveri

2023

Molecules

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Amyloid diseases have become a global concern due to their increasing prevalence. Transition metals, including copper, can affect the aggregation of the pathological proteins involved in these diseases. Copper ions play vital roles in organisms, but the disruption of their homeostasis can negatively impact neuronal function and contribute to amyloid diseases with toxic protein aggregates, oxidative stress, mitochondrial dysfunction, impaired cellular signaling, inflammation, and cell death. Gaining insight into the imbalance of copper ions and its impact on protein folding and aggregation is crucial for developing focused therapies. This review examines the influence of copper ions on significant amyloid proteins/peptides, offering a comprehensive overview of the current understanding in this field.

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Section: Factors Influencing Protein Aggregationmentioning

confidence: 99%

Unveiling the Effects of Copper Ions in the Aggregation of Amyloidogenic Proteins

Oliveri

2023

Molecules

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“…Beta-synuclein binds to metals to regulate cellular metal homeostasis, particularly chelated copper ions, which can produce free radicals and promote the formation of cytotoxic alpha-synuclein oligomers [ 11 , 53 , 54 ]. There is also a suggestion that beta-synuclein can affect the autophagic–lysosomal pathway, removing damaged or toxic protein molecules and even aggregates [ 55 , 56 ].…”

Section: Synuclein Structure and Functionsmentioning

confidence: 99%

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2022

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Parkinson’s disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family. Here, we review research from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity models and various synuclein-knockout animals. We conclude that the differences in the sensitivity of the synuclein-knockout animals compared with the MPTP neurotoxin are due to the ontogenetic selection of early neurons followed by a compensatory effect of beta-synuclein, which optimizes dopamine capture in the synapses. Triple-knockout synuclein studies have confirmed the higher sensitivity of DA neurons to the toxic effects of MPTP. Nonetheless, beta-synuclein could modulate the alpha-synuclein function, preventing its aggregation and loss of function. Overall, the use of knockout animals has helped to solve the riddle of synuclein functions, and these proteins could be promising molecular targets for the development of therapies that are aimed at optimizing the synaptic function of dopaminergic neurons.

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Comparing the copper binding features of alpha and beta synucleins

Cited by 2 publications

References 42 publications

Unveiling the Effects of Copper Ions in the Aggregation of Amyloidogenic Proteins

Unveiling the Effects of Copper Ions in the Aggregation of Amyloidogenic Proteins

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

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