Parkinson’s Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances

Hill, David R.; Huters, Alexander D.; Towne, Timothy B.; Reddy, Rajarathnam E.; Fogle, Jace L.; Voight, Eric A.; Kym, Philip R.

doi:10.1021/acs.chemrev.3c00479

Cited by 10 publications

(11 citation statements)

References 86 publications

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“…Currently, the pharmacotherapy for AD and PD consists of drugs approved by the Food and Drug Administration (FDA) that regulate neurotransmitter levels. Unfortunately, they only provide valuable but modest symptomatic benefits, being unable to modify the course of these diseases [ 9 , 150 ]. These treatments are also accompanied by limitations.…”

Section: Pharmacotherapy Of Alzheimer’s and Parkinson’s Diseasesmentioning

confidence: 99%

“…Despite the intensive research performed so far, to date, no breakthrough treatment has been discovered. The available therapies for NDs only provide symptomatic and palliative relief for a limited period [ 7 ] and are unable to modify the disease progression [ 8 , 9 ]. Therefore, the development of disease-modifying drugs able to prevent, halt or reverse the progression of NDs remains an unmet clinical need.…”

Section: Introductionmentioning

confidence: 99%

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Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Sequeira,

Benfeito,

Fernandes

et al. 2024

Pharmaceutics

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Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

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Section: Pharmacotherapy Of Alzheimer’s and Parkinson’s Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Sequeira,

Benfeito,

Fernandes

et al. 2024

Pharmaceutics

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“…Parkinson’s disease (PD) is a common neurodegenerative disease that mainly does severe harm to the health of the elderly. Its typical symptoms include resting tremors, bradykinesia, muscle rigidity, and postural instability. − Although the underlying mechanisms of PD are not clarified yet, increasing attention has been paid to the loss of dopaminergic neurons, − particularly the loss of tyrosine hydroxylase (TH)-positive neurons. − TH is a key enzyme for producing dopamine, which is a neurotransmitter that transfers signals to the nervous system. Dopaminergic neurons in PD gradually degenerate, leading to a decrease in dopamine levels and a series of PD symptoms. , Therefore, TH levels can serve as an indicator for assessing the severity and progression of PD.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe

Yao,

Li,

et al. 2024

Anal. Chem.

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Parkinson's disease (PD) represents the second most widespread neurodegenerative disease, and early monitoring and diagnosis are urgent at present. Tyrosine hydroxylase (TH) is a key enzyme for producing dopamine, the levels of which can serve as an indicator for assessing the severity and progression of PD. This renders the specific detection and visualization of TH a strategically vital way to meet the above demands. However, a fluorescent probe for TH monitoring is still missing. Herein, three rationally designed wash-free ratiometric fluorescent probes were proposed. Among them, TH-1 exhibited ideal photophysical properties and specific dual-channel bioimaging of TH activity in SH-SY5Y nerve cells. Moreover, the probe allowed for in vivo imaging of TH activity in zebrafish brain and living striatal slices of mice. Overall, the ratiometric fluorescent probe TH-1 could serve as a potential tool for real-time monitoring of PD in complex biosystems.

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“…With the rapid development of medicinal and natural product chemistry, the diversity and complexity of organic molecules are increasing [ 1 , 2 , 3 , 4 , 5 , 6 ]. Therefore, developing efficient organic synthesis strategies to cope with this situation is very necessary.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Domino Annulation Reaction of Quinone Imines

Wang,

Fu,

et al. 2024

Molecules

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Quinone imines are important derivatives of quinones with a wide range of applications in organic synthesis and the pharmaceutical industry. The attack of nucleophilic reagents on quinone imines tends to lead to aromatization of the quinone skeleton, resulting in both the high reactivity and the unique reactivity of quinone imines. The extreme value of quinone imines in the construction of nitrogen- or oxygen-containing heterocycles has attracted widespread attention, and remarkable advances have been reported recently. This review provides an overview of the application of quinone imines in the synthesis of cyclic compounds via the domino annulation reaction.

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Parkinson’s Disease: Advances in Treatment and the Syntheses of Various Classes of Pharmaceutical Drug Substances

Cited by 10 publications

References 86 publications

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Real-Time Monitoring of Tyrosine Hydroxylase Activity with a Ratiometric Fluorescent Probe

Recent Advances in the Domino Annulation Reaction of Quinone Imines

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