The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging
The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/5/763 |
| _version_ | 1797615586494119936 |
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| author | Lana Kupershmidt Moussa B. H. Youdim |
| author_facet | Lana Kupershmidt Moussa B. H. Youdim |
| author_sort | Lana Kupershmidt |
| collection | DOAJ |
| description | The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated. |
| first_indexed | 2024-03-11T07:28:42Z |
| format | Article |
| id | doaj.art-7094acdfd2994c2e911a957919e2a4f7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T07:28:42Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7094acdfd2994c2e911a957919e2a4f72023-11-17T07:27:49ZengMDPI AGCells2073-44092023-02-0112576310.3390/cells12050763The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and AgingLana Kupershmidt0Moussa B. H. Youdim1Clinical Research Institute at Rambam Health Care, Haifa 31096, IsraelTechnion-Rappaport Family Faculty of Medicine, Haifa 31096, IsraelThe concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated.https://www.mdpi.com/2073-4409/12/5/763Alzheimer’s diseaseamyotrophic lateral sclerosisoxidative stressmonoamine oxidaseironiron chelator |
| spellingShingle | Lana Kupershmidt Moussa B. H. Youdim The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging Cells Alzheimer’s disease amyotrophic lateral sclerosis oxidative stress monoamine oxidase iron iron chelator |
| title | The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging |
| title_full | The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging |
| title_fullStr | The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging |
| title_full_unstemmed | The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging |
| title_short | The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis and Aging |
| title_sort | neuroprotective activities of the novel multi target iron chelators in models of alzheimer s disease amyotrophic lateral sclerosis and aging |
| topic | Alzheimer’s disease amyotrophic lateral sclerosis oxidative stress monoamine oxidase iron iron chelator |
| url | https://www.mdpi.com/2073-4409/12/5/763 |
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