Are dopamine derivatives implicated in the pathogenesis of Parkinson's disease?
•The molecular pathways involved in Parkinson's disease are extensively described.•The aforementioned pathways are linked to the oxidative chemistry of dopamine.•The reactions of dopamine-derived quinones with cellular targets are emphasized.•Dopamine-derived quinones could contribute to the pr...
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| Published in | Ageing research reviews Vol. 13; pp. 107 - 114 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Amsterdam
Elsevier B.V
01.01.2014
Elsevier |
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| Abstract | •The molecular pathways involved in Parkinson's disease are extensively described.•The aforementioned pathways are linked to the oxidative chemistry of dopamine.•The reactions of dopamine-derived quinones with cellular targets are emphasized.•Dopamine-derived quinones could contribute to the progression of Parkinson's disease.
Parkinson's disease (PD) is the most common motor system disorder affecting 1–2% of people over the age of sixty-five. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5–10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. These mechanisms include impairment of the intracellular protein-degradation pathways, protein aggregation, mitochondria dysfunction, oxidative stress and neuroinflammation. Some of these features are also supported by post-mortem analyses. One of the main pathological hallmarks of PD is the preferential degeneration of dopaminergic neurons, which supports a direct role of dopamine itself in promoting the disorder. This review presents a comprehensive overview of the existing literature that links the aforementioned pathways to the oxidative chemistry of dopamine, ultimately leading to the formation of free radicals and reactive quinone species. We emphasize, in particular, how the reaction of dopamine-derived quinones with several cellular targets could foster the processes involved in the pathogenesis of PD and contribute to the progression of the disorder. |
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| AbstractList | •The molecular pathways involved in Parkinson's disease are extensively described.•The aforementioned pathways are linked to the oxidative chemistry of dopamine.•The reactions of dopamine-derived quinones with cellular targets are emphasized.•Dopamine-derived quinones could contribute to the progression of Parkinson's disease.
Parkinson's disease (PD) is the most common motor system disorder affecting 1–2% of people over the age of sixty-five. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5–10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. These mechanisms include impairment of the intracellular protein-degradation pathways, protein aggregation, mitochondria dysfunction, oxidative stress and neuroinflammation. Some of these features are also supported by post-mortem analyses. One of the main pathological hallmarks of PD is the preferential degeneration of dopaminergic neurons, which supports a direct role of dopamine itself in promoting the disorder. This review presents a comprehensive overview of the existing literature that links the aforementioned pathways to the oxidative chemistry of dopamine, ultimately leading to the formation of free radicals and reactive quinone species. We emphasize, in particular, how the reaction of dopamine-derived quinones with several cellular targets could foster the processes involved in the pathogenesis of PD and contribute to the progression of the disorder. Highlights • The molecular pathways involved in Parkinson's disease are extensively described. • The aforementioned pathways are linked to the oxidative chemistry of dopamine. • The reactions of dopamine-derived quinones with cellular targets are emphasized. • Dopamine-derived quinones could contribute to the progression of Parkinson's disease. Parkinson's disease (PD) is the most common motor system disorder affecting 1-2% of people over the age of sixty-five. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5-10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. These mechanisms include impairment of the intracellular protein-degradation pathways, protein aggregation, mitochondria dysfunction, oxidative stress and neuroinflammation. Some of these features are also supported by post-mortem analyses. One of the main pathological hallmarks of PD is the preferential degeneration of dopaminergic neurons, which supports a direct role of dopamine itself in promoting the disorder. This review presents a comprehensive overview of the existing literature that links the aforementioned pathways to the oxidative chemistry of dopamine, ultimately leading to the formation of free radicals and reactive quinone species. We emphasize, in particular, how the reaction of dopamine-derived quinones with several cellular targets could foster the processes involved in the pathogenesis of PD and contribute to the progression of the disorder. Parkinson's disease (PD) is the most common motor system disorder affecting 1-2% of people over the age of sixty-five. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5-10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. These mechanisms include impairment of the intracellular protein-degradation pathways, protein aggregation, mitochondria dysfunction, oxidative stress and neuroinflammation. Some of these features are also supported by post-mortem analyses. One of the main pathological hallmarks of PD is the preferential degeneration of dopaminergic neurons, which supports a direct role of dopamine itself in promoting the disorder. This review presents a comprehensive overview of the existing literature that links the aforementioned pathways to the oxidative chemistry of dopamine, ultimately leading to the formation of free radicals and reactive quinone species. We emphasize, in particular, how the reaction of dopamine-derived quinones with several cellular targets could foster the processes involved in the pathogenesis of PD and contribute to the progression of the disorder.Parkinson's disease (PD) is the most common motor system disorder affecting 1-2% of people over the age of sixty-five. Although PD is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease, representing 5-10% of all cases, has been very important in helping to partially delineate the molecular pathways that lead to this pathology. These mechanisms include impairment of the intracellular protein-degradation pathways, protein aggregation, mitochondria dysfunction, oxidative stress and neuroinflammation. Some of these features are also supported by post-mortem analyses. One of the main pathological hallmarks of PD is the preferential degeneration of dopaminergic neurons, which supports a direct role of dopamine itself in promoting the disorder. This review presents a comprehensive overview of the existing literature that links the aforementioned pathways to the oxidative chemistry of dopamine, ultimately leading to the formation of free radicals and reactive quinone species. We emphasize, in particular, how the reaction of dopamine-derived quinones with several cellular targets could foster the processes involved in the pathogenesis of PD and contribute to the progression of the disorder. |
| Author | Filograna, Roberta Bisaglia, Marco Bubacco, Luigi Beltramini, Mariano |
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| Copyright | 2014 Elsevier B.V. Elsevier B.V. 2015 INIST-CNRS Copyright © 2014 Elsevier B.V. All rights reserved. |
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| Keywords | Oxidative stress Mitochondria Dopamine Parkinson's disease Dopamine-quinones Sporadic Pathogenesis Motor system disorder Parkinson disease Discoveries Mechanism Aggregation Degradation Degenerative disease Neurological disorder Age Human Nervous system diseases Neuroinflammation Catecholamine Monogenic Protein Cerebral disorder Anatomic pathology Dysfunction Central nervous system disease Neurotransmitter Intracellular Extrapyramidal syndrome |
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| Snippet | •The molecular pathways involved in Parkinson's disease are extensively described.•The aforementioned pathways are linked to the oxidative chemistry of... Highlights • The molecular pathways involved in Parkinson's disease are extensively described. • The aforementioned pathways are linked to the oxidative... Parkinson's disease (PD) is the most common motor system disorder affecting 1-2% of people over the age of sixty-five. Although PD is generally a sporadic... |
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| SubjectTerms | Animals Biological and medical sciences Brain - metabolism Brain - pathology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Development. Metamorphosis. Moult. Ageing Disease Progression Dopamine Dopamine - analogs & derivatives Dopamine - metabolism Dopamine-quinones Dopaminergic Neurons - metabolism Dopaminergic Neurons - pathology Fundamental and applied biological sciences. Psychology Humans Internal Medicine Medical sciences Mitochondria Mitochondria - metabolism Nerve Degeneration Nervous system (semeiology, syndromes) Nervous system as a whole Neurology Oxidation-Reduction Oxidative Stress Parkinson Disease - genetics Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson's disease Signal Transduction Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| Title | Are dopamine derivatives implicated in the pathogenesis of Parkinson's disease? |
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