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Review
. 2022 Jun 4;12(6):785.
doi: 10.3390/biom12060785.

Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases

Hui-Liang Zhang  1 , Xiao-Chuan Wang  1 , Rong Liu  1
Affiliations
Review

Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases

Hui-Liang Zhang et al. Biomolecules. .

Abstract

Zinc is essential for human growth and development. As a trace nutrient, zinc plays important roles in numerous signal transduction pathways involved in distinct physiologic or pathologic processes. Protein phosphorylation is a posttranslational modification which regulates protein activity, degradation, and interaction with other molecules. Protein kinases (PKs) and phosphatases (PPs), with their effects of adding phosphate to or removing phosphate from certain substrates, are master regulators in controlling the phosphorylation of proteins. In this review, we summarize the disturbance of zinc homeostasis and role of zinc disturbance in regulating protein kinases and protein phosphatases in neurodegenerative diseases, with the focus of that in Alzheimer's disease, providing a new perspective for understanding the mechanisms of these neurologic diseases.

Keywords: Alzheimer’s disease; neurodegenerative diseases; protein kinases; protein phosphatases; zinc.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of zinc in the body. Dietary zinc is absorbed by the digestive system and then distributed to peripheral tissues. Approximately 60% of zinc is stored in skeletal muscle, 30% in bone, and 5% in liver and skin. Excess zinc is excreted through gastrointestinal secretions and mucosal cells. Brain zinc levels change in patients with neurodegenerative diseases such as PD, ALS, and AD.
Figure 2
Figure 2
Protein kinases (PKs) and protein phosphatases (PPs) of tau regulated by zinc in AD. Elevated zinc causes activation of kinases (GSK-3β, CDK5, MAPK, PKA, PKC) and simultaneous inhibition of phosphatases (PP-2A, PP-2B), leading to tau pathogenesis; the inhibition of PP-2A and activation of JNK, CDK5 also promote APP hyperphosphorylation and Aβ deposition, ultimately resulting in neuronal damage and disease development. Solid lines indicate there is known evidence from literatures, and dashed lines indicate that direct evidence is still absent, but current data support the hypothesis.
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