The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease
Alzheimer’s disease (AD) is one of the most frequently diagnosed types of dementia in the elderly. An important pathological feature in AD is the aggregation and deposition of the β-amyloid (Aβ) in extracellular plaques. Transthyretin (TTR) can cleave Aβ, resulting in the formation of short peptides...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/23/9003 |
| _version_ | 1797546578217533440 |
|---|---|
| author | Natalia Zaręba Marta Kepinska |
| author_facet | Natalia Zaręba Marta Kepinska |
| author_sort | Natalia Zaręba |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is one of the most frequently diagnosed types of dementia in the elderly. An important pathological feature in AD is the aggregation and deposition of the β-amyloid (Aβ) in extracellular plaques. Transthyretin (TTR) can cleave Aβ, resulting in the formation of short peptides with less activity of amyloid plaques formation, as well as being able to degrade Aβ peptides that have already been aggregated. In the presence of TTR, Aβ aggregation decreases and toxicity of Aβ is abolished. This may prevent amyloidosis but the malfunction of this process leads to the development of AD. In the context of Aβplaque formation in AD, we discuss metallothionein (MT) interaction with TTR, the effects of which depend on the type of MT isoform. In the brains of patients with AD, the loss of MT-3 occurs. On the contrary, MT-1/2 level has been consistently reported to be increased. Through interaction with TTR, MT-2 reduces the ability of TTR to bind to Aβ, while MT-3 causes the opposite effect. It increases TTR-Aβ binding, providing inhibition of Aβ aggregation. The protective effect, assigned to MT-3 against the deposition of Aβ, relies also on this mechanism. Additionally, both Zn<sub>7</sub>MT-2 and Zn<sub>7</sub>MT-3, decrease Aβ neurotoxicity in cultured cortical neurons probably because of a metal swap between Zn<sub>7</sub>MT and Cu(II)Aβ. Understanding the molecular mechanism of metals transfer between MT and other proteins as well as cognition of the significance of TTR interaction with different MT isoforms can help in AD treatment and prevention. |
| first_indexed | 2024-03-10T14:31:48Z |
| format | Article |
| id | doaj.art-2c7d44f1d04547e2beb5311ed4506c74 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:31:48Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2c7d44f1d04547e2beb5311ed4506c742023-11-20T22:31:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123900310.3390/ijms21239003The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s DiseaseNatalia Zaręba0Marta Kepinska1Department of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, PolandDepartment of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, PolandAlzheimer’s disease (AD) is one of the most frequently diagnosed types of dementia in the elderly. An important pathological feature in AD is the aggregation and deposition of the β-amyloid (Aβ) in extracellular plaques. Transthyretin (TTR) can cleave Aβ, resulting in the formation of short peptides with less activity of amyloid plaques formation, as well as being able to degrade Aβ peptides that have already been aggregated. In the presence of TTR, Aβ aggregation decreases and toxicity of Aβ is abolished. This may prevent amyloidosis but the malfunction of this process leads to the development of AD. In the context of Aβplaque formation in AD, we discuss metallothionein (MT) interaction with TTR, the effects of which depend on the type of MT isoform. In the brains of patients with AD, the loss of MT-3 occurs. On the contrary, MT-1/2 level has been consistently reported to be increased. Through interaction with TTR, MT-2 reduces the ability of TTR to bind to Aβ, while MT-3 causes the opposite effect. It increases TTR-Aβ binding, providing inhibition of Aβ aggregation. The protective effect, assigned to MT-3 against the deposition of Aβ, relies also on this mechanism. Additionally, both Zn<sub>7</sub>MT-2 and Zn<sub>7</sub>MT-3, decrease Aβ neurotoxicity in cultured cortical neurons probably because of a metal swap between Zn<sub>7</sub>MT and Cu(II)Aβ. Understanding the molecular mechanism of metals transfer between MT and other proteins as well as cognition of the significance of TTR interaction with different MT isoforms can help in AD treatment and prevention.https://www.mdpi.com/1422-0067/21/23/9003Alzheimer’s diseaseβ-amyloidmetallothioneinprotein-protein interactiontransthyretin |
| spellingShingle | Natalia Zaręba Marta Kepinska The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease β-amyloid metallothionein protein-protein interaction transthyretin |
| title | The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease |
| title_full | The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease |
| title_fullStr | The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease |
| title_full_unstemmed | The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease |
| title_short | The Function of Transthyretin Complexes with Metallothionein in Alzheimer’s Disease |
| title_sort | function of transthyretin complexes with metallothionein in alzheimer s disease |
| topic | Alzheimer’s disease β-amyloid metallothionein protein-protein interaction transthyretin |
| url | https://www.mdpi.com/1422-0067/21/23/9003 |
| work_keys_str_mv | AT nataliazareba thefunctionoftransthyretincomplexeswithmetallothioneininalzheimersdisease AT martakepinska thefunctionoftransthyretincomplexeswithmetallothioneininalzheimersdisease AT nataliazareba functionoftransthyretincomplexeswithmetallothioneininalzheimersdisease AT martakepinska functionoftransthyretincomplexeswithmetallothioneininalzheimersdisease |