Cross talk between neurometals and amyloidogenic proteins at the synapse and the pathogenesis of neurodegenerative diseases.
Abstract
Increasing evidence suggests that disruption of metal homeostasis contributes to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, prion diseases, Lewy body diseases, and vascular dementia. Conformational changes of disease-related proteins (amyloidogenic proteins), such as β-amyloid protein, prion proteins, and α-synuclein, are well-established contributors to neurotoxicity and to the pathogenesis of these diseases. Recent studies have demonstrated that these amyloidogenic proteins are metalloproteins that bind trace elements, including zinc, iron, copper, and manganese, and play significant roles in the maintenance of metal homeostasis. We present a current review of the role of trace elements in the functions and toxicity of amyloidogenic proteins, and propose a hypothesis integrating metal homeostasis and the pathogenesis of neurodegenerative diseases that is focused on the interactions among metals and between metals and amyloidogenic proteins at the synapse, considering that these amyloidogenic proteins and metals are co-localized at the synapse.
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Many individuals are likely to develop LOAD due to a combination of genetic and environmental factors.
“Studies also suggest that genetic factors may only contribute between 50 and 70% of the risk for LOAD, meaning many individuals are likely to develop LOAD due to a combination of genetic and environmental factors (Kawahara et al., 2017; Sarkar et al., 2019; Rahman et al., 2020; Kim et al., 2021).”
From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Kawahara et al., 2017
Genetic factors may contribute only between 50 and 70% of the risk for LOAD.
“Studies also suggest that genetic factors may only contribute between 50 and 70% of the risk for LOAD, meaning many individuals are likely to develop LOAD due to a combination of genetic and environmental factors (Kawahara et al., 2017; Sarkar et al., 2019; Rahman et al., 2020; Kim et al., 2021).”
From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Kawahara et al., 2017
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The role of zinc, copper, manganese and iron in neurodegenerative diseases
Mezzaroba, L., Alfieri, D. F., Colado Simão, A. N., & Vissoci Reiche, E. M. (2019) · NeuroToxicology · doi:10.1016/j.neuro.2019.07.007 · Cited by 524 · see citing works
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- Authors
- Kawahara, M., Kato-Negishi, M., & Tanaka, K.
- Affiliations
- Musashino University (JP)
- Corresponding author
- Kawahara, M.
- Venue
- Metallomics
- Publisher
- Oxford University Press (OUP)
- Published
- 2017
- Volume
- 9
- Issue
- 6
- Pages
- 619-633
- ISSN
- 1756-5901 (ISSN-L)
- 1756-591X
- OpenAlex
- W2609523813
- Cited by
- 80
- References
- 6
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 10 · 2023: 9 · 2022: 12 · 2021: 4 · 2020: 13 · 2019: 6 · 2018: 10 · 2017: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metallomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26460177)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- metal homeostasis, trace elements, amyloidogenic proteins, synapses, neurodegenerative diseases, Alzheimer's disease, prion disease, Lewy body disease, vascular dementia, zinc, iron, copper, manganese, metalloproteins, protein conformational change, neurotoxicity, metal-protein interactions
- MeSH terms
- Humans, Synapses, Trace Elements, Neurodegenerative Diseases, Amyloidogenic Proteins
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