To what extent may aminochrome increase the vulnerability of dopaminergic neurons in the context of Parkinson's disease

Chagraoui, Abdeslam; Anouar, Youssef; De Deurwaerdere, Philippe; Arias, Hugo R.

doi:10.1016/j.biocel.2024.106528

Cited by 3 publications

(2 citation statements)

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“…These ortho-quinones are potentially neurotoxic but aminochrome is the most stable and neurotoxic [65,66]. Aminochrome induces oxidative stress, mitochondrial dysfunction, formation of neurotoxic alpha-synuclein oligomers, dysfunction of both lysosomal and proteasomal protein degradation systems, neuroinflammation, and endoplasmic reticulum stress [67][68][69][70][71][72].…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Finally, this redox cycling generates oxidative stress and ATP depletion that is required, among other things, for the neurotransmission of dopamine from monoaminergic vesicles; and (ii) aminochrome is also capable of forming adducts with proteins such as alpha-synuclein, actin, α and β-tubulin, mitochondrial complex 1, ATP13A, and other proteins [62,86,87]. The neurotoxic effects of aminochrome induce oxidative stress, neuroinflammation, formation of neurotoxic alpha-synuclein oligomers, mitochondrial dysfunction, endoplasmic reticulum stress, and dysfunction of both lysosomal and proteasomal protein degradation systems [67][68][69][70][71][72].…”

Section: Dopamine Metabolismmentioning

confidence: 99%

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Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model

Huenchuguala,

Segura-Aguilar

2024

Biomolecules

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One of the biggest problems in the treatment of idiopathic Parkinson’s disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for idiopathic Parkinson’s disease that requires years to accumulate enough lost neurons for the onset of motor symptoms. This single-neuron degeneration model is based on the excessive formation of aminochrome during neuromelanin synthesis that surpass the neuroprotective action of the enzymes DT-diaphorase and glutathione transferase M2-2, which prevent the neurotoxic effects of aminochrome. Although the neurotoxic effects of aminochrome do not have an expansive effect, a stereotaxic injection of this endogenous neurotoxin cannot be used to generate a preclinical model in an animal. Therefore, the aim of this review is to evaluate the strategies for pharmacologically increasing the expression of DT diaphorase and GSTM2-2 and molecules that induce the expression of vesicular monoamine transporter 2, such as pramipexole.

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