On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease
Protein aggregation, mitochondrial dysfunction, iron dyshomeostasis, increased oxidative damage and inflammation are pathognomonic features of Parkinson’s disease (PD) and other neurodegenerative disorders characterized by abnormal iron accumulation. Moreover, the existence of positive feed-back loo...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/2/214 |
| _version_ | 1797622684183429120 |
|---|---|
| author | Olimpo García-Beltrán Pamela J. Urrutia Marco T. Núñez |
| author_facet | Olimpo García-Beltrán Pamela J. Urrutia Marco T. Núñez |
| author_sort | Olimpo García-Beltrán |
| collection | DOAJ |
| description | Protein aggregation, mitochondrial dysfunction, iron dyshomeostasis, increased oxidative damage and inflammation are pathognomonic features of Parkinson’s disease (PD) and other neurodegenerative disorders characterized by abnormal iron accumulation. Moreover, the existence of positive feed-back loops between these pathological components, which accelerate, and sometimes make irreversible, the neurodegenerative process, is apparent. At present, the available treatments for PD aim to relieve the symptoms, thus improving quality of life, but no treatments to stop the progression of the disease are available. Recently, the use of multifunctional compounds with the capacity to attack several of the key components of neurodegenerative processes has been proposed as a strategy to slow down the progression of neurodegenerative processes. For the treatment of PD specifically, the necessary properties of new-generation drugs should include mitochondrial destination, the center of iron-reactive oxygen species interaction, iron chelation capacity to decrease iron-mediated oxidative damage, the capacity to quench free radicals to decrease the risk of ferroptotic neuronal death, the capacity to disrupt α-synuclein aggregates and the capacity to decrease inflammatory conditions. Desirable additional characteristics are dopaminergic neurons to lessen unwanted secondary effects during long-term treatment, and the inhibition of the MAO-B and COMPT activities to increase intraneuronal dopamine content. On the basis of the published evidence, in this work, we review the molecular basis underlying the pathological events associated with PD and the clinical trials that have used single-target drugs to stop the progress of the disease. We also review the current information on multifunctional compounds that may be used for the treatment of PD and discuss the chemical characteristics that underlie their functionality. As a projection, some of these compounds or modifications could be used to treat diseases that share common pathology features with PD, such as Friedreich’s ataxia, Multiple sclerosis, Huntington disease and Alzheimer’s disease. |
| first_indexed | 2024-03-11T09:14:44Z |
| format | Article |
| id | doaj.art-1d7d30cd1951413a87391120ce20c221 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T09:14:44Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1d7d30cd1951413a87391120ce20c2212023-11-16T18:44:57ZengMDPI AGAntioxidants2076-39212023-01-0112221410.3390/antiox12020214On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s DiseaseOlimpo García-Beltrán0Pamela J. Urrutia1Marco T. Núñez2Facultad de Ciencias Naturales y Matemáticas, Universidad de Ibagué, Carrera 22 Calle 67, Ibagué 730002, ColombiaFaculty of Medicine and Science, Universidad San Sebastián, Lota 2465, Santiago 7510157, ChileFaculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago 7800024, ChileProtein aggregation, mitochondrial dysfunction, iron dyshomeostasis, increased oxidative damage and inflammation are pathognomonic features of Parkinson’s disease (PD) and other neurodegenerative disorders characterized by abnormal iron accumulation. Moreover, the existence of positive feed-back loops between these pathological components, which accelerate, and sometimes make irreversible, the neurodegenerative process, is apparent. At present, the available treatments for PD aim to relieve the symptoms, thus improving quality of life, but no treatments to stop the progression of the disease are available. Recently, the use of multifunctional compounds with the capacity to attack several of the key components of neurodegenerative processes has been proposed as a strategy to slow down the progression of neurodegenerative processes. For the treatment of PD specifically, the necessary properties of new-generation drugs should include mitochondrial destination, the center of iron-reactive oxygen species interaction, iron chelation capacity to decrease iron-mediated oxidative damage, the capacity to quench free radicals to decrease the risk of ferroptotic neuronal death, the capacity to disrupt α-synuclein aggregates and the capacity to decrease inflammatory conditions. Desirable additional characteristics are dopaminergic neurons to lessen unwanted secondary effects during long-term treatment, and the inhibition of the MAO-B and COMPT activities to increase intraneuronal dopamine content. On the basis of the published evidence, in this work, we review the molecular basis underlying the pathological events associated with PD and the clinical trials that have used single-target drugs to stop the progress of the disease. We also review the current information on multifunctional compounds that may be used for the treatment of PD and discuss the chemical characteristics that underlie their functionality. As a projection, some of these compounds or modifications could be used to treat diseases that share common pathology features with PD, such as Friedreich’s ataxia, Multiple sclerosis, Huntington disease and Alzheimer’s disease.https://www.mdpi.com/2076-3921/12/2/214Parkinson’s diseaseiron dyshomeostasisclinical trialsmultifunctional drugs |
| spellingShingle | Olimpo García-Beltrán Pamela J. Urrutia Marco T. Núñez On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease Antioxidants Parkinson’s disease iron dyshomeostasis clinical trials multifunctional drugs |
| title | On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease |
| title_full | On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease |
| title_fullStr | On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease |
| title_full_unstemmed | On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease |
| title_short | On the Chemical and Biological Characteristics of Multifunctional Compounds for the Treatment of Parkinson’s Disease |
| title_sort | on the chemical and biological characteristics of multifunctional compounds for the treatment of parkinson s disease |
| topic | Parkinson’s disease iron dyshomeostasis clinical trials multifunctional drugs |
| url | https://www.mdpi.com/2076-3921/12/2/214 |
| work_keys_str_mv | AT olimpogarciabeltran onthechemicalandbiologicalcharacteristicsofmultifunctionalcompoundsforthetreatmentofparkinsonsdisease AT pamelajurrutia onthechemicalandbiologicalcharacteristicsofmultifunctionalcompoundsforthetreatmentofparkinsonsdisease AT marcotnunez onthechemicalandbiologicalcharacteristicsofmultifunctionalcompoundsforthetreatmentofparkinsonsdisease |