Grundlagen und Stellenwert der COMT- und MAO-B-Inhibitoren in der Therapie des idiopathischen Parkinson-Syndroms

Woitalla, Dirk; Krüger, Rejko; Lorenzl, Stefan; Müller, Thomas; Oelwein, Guenther; Storch, Alexander; Wolz, Martin; Wüllner, Ullrich

doi:10.1055/a-1149-9308

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…They retard the degradation of L-DOPA and DA, stabilizing the concentration level of endogenous DA [ 238 ]. Of note, the COMT inhibitor is only used in combination with L-DOPA [ 239 ].…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

2023

Aging dis

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Vestigial dopaminergic cells in PD have selectivity for a sub-class of hypersensitive neurons with the nigrostriatal dopamine (DA) tract. DA is modulated in pre-synaptic nerve terminals to remain stable. To be specific, proteins at DA release sites that have a function of synthesizing and packing DA in cytoplasm, modulating release and reingestion, and changing excitability of neurons, display regional discrepancies that uncover relevancy of the observed sensitivity to neurodegenerative changes. Although the reasons of a majority of PD cases are still indistinct, heredity and environment are known to us to make significant influences. For decades, genetic analysis of PD patients with heredity in family have promoted our comprehension of pathogenesis to a great extent, which reveals correlative mechanisms including oxidative stress, abnormal protein homeostasis and mitochondrial dysfunction. In this review, we review the constitution of presynaptic vesicle related to DA homeostasis and describe the genetic and environmental evidence of presynaptic dysfunction that increase risky possibility of PD concerning intracellular vesicle transmission and their functional outcomes. We summarize alterations in synaptic vesicular proteins with great involvement in the reasons of some DA neurons highly vulnerable to neurodegenerative changes. We generalize different potential targets and therapeutic strategies for different pathogenic mechanisms, providing a reference for further studies of PD treatment in the future. But it remains to be further researched on this recently discovered and converging mechanism of vesicular dynamics and PD, which will provide a more profound comprehension and put up with new therapeutic tactics for PD patients.

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“…They retard the degradation of L-DOPA and DA, stabilizing the concentration level of endogenous DA [ 238 ]. Of note, the COMT inhibitor is only used in combination with L-DOPA [ 239 ].…”

Section: Therapeutic Implications and Future Directionsmentioning

confidence: 99%

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

2023

Aging dis

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Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds

Melfi

Carradori

Angeli

et al. 2023

Expert Opinion on Drug Discovery

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Levodopa-Induced Dyskinesia in Parkinson’s Disease: Pathogenesis and Emerging Treatment Strategies

Kwon

Kwatra

Wang

et al. 2022

Cells

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The most commonly used treatment for Parkinson’s disease (PD) is levodopa, prescribed in conjunction with carbidopa. Virtually all patients with PD undergo dopamine replacement therapy using levodopa during the course of the disease’s progression. However, despite the fact that levodopa is the “gold standard” in PD treatments and has the ability to significantly alleviate PD symptoms, it comes with side effects in advanced PD. Levodopa replacement therapy remains the current clinical treatment of choice for Parkinson’s patients, but approximately 80% of the treated PD patients develop levodopa-induced dyskinesia (LID) in the advanced stages of the disease. A better understanding of the pathological mechanisms of LID and possible means of improvement would significantly improve the outcome of PD patients, reduce the complexity of medication use, and lower adverse effects, thus, improving the quality of life of patients and prolonging their life cycle. This review assesses the recent advancements in understanding the underlying mechanisms of LID and the therapeutic management options available after the emergence of LID in patients. We summarized the pathogenesis and the new treatments for LID-related PD and concluded that targeting pathways other than the dopaminergic pathway to treat LID has become a new possibility, and, currently, amantadine, drugs targeting 5-hydroxytryptamine receptors, and surgery for PD can target the Parkinson’s symptoms caused by LID.

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Grundlagen und Stellenwert der COMT- und MAO-B-Inhibitoren in der Therapie des idiopathischen Parkinson-Syndroms

Cited by 3 publications

References 58 publications

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson’s Disease Pathogenesis

Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds

Levodopa-Induced Dyskinesia in Parkinson’s Disease: Pathogenesis and Emerging Treatment Strategies

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