. 2022 Jul 18;12(7):1000. doi: 10.3390/biom12071000

Table 1.

The molecular mechanism and function of ZnTs and MTs in ARCD.

Zinc Associated Protein		Function	Reference
Zinc transporters	ZnT-1	Limit the accumulation of postsynaptic Zn²⁺ after translocation from presynaptic release sites Protect neurons from Zn²⁺ toxicity As a Zn^2+/H+ exchanger in acidic cells, it inhibits ZnT-1 dependent Zn²⁺ outflow in neurons ZnT-1 is elevated in AD patients, making Aβ gather	[104,110,112,113,114,115]
	ZnT-3	Transport Zn²⁺ from cytoplasm to SVs and regulate the concentration of Zn²⁺ in SVs Co-localization with VGLUT1 increased the content of glutamate in VTs and the postsynaptic response Maintain Zn2þ homeostasis in synapses, so as to maintain human cognitive function Plasma and neurons depend on it to exchange through the blood vessel wall	[117,118,119,120,123,124,125]
	ZnT-4	Increase the concentration of Zn²⁺ in SVs, promote the transport of Zn²⁺ to endosomes and lysosomes, and protect neurons from zinc poisoning Accelerate the accumulation of Aβ in the brain of patients with AD Further damage the BBB in patients with is, and damage the neural cells and glial cells related to cognition	[127,128,129,131,132,133,135]
	ZnT-6	It separates Zn²⁺ in the cytoplasm into TGN and VTs in cells with high Zn concentration It plays a transport or secretory function on the plasma membrane, destroys the normal sorting and transport of essential proteins and lipids, and leads to neuronal degeneration and cytoplasmic inclusion Activate smpd1 to promote sphingolipid metabolism and convert sphingomyelin into ceramide and choline phosphate	[114,136,137]
Metallothionein	MT-I/MT-II	Maintain intracellular homeostasis of essential metal ions in the human body Induced by oxidative stress in human astrocytes In AD patients, MT-I directly attenuates the neurotoxicity of Aβ and indirectly inhibits Aβ-induced microglia activation and subsequent neurotoxicity Prevention of dopamine quinone induced neurotoxicity in patients with Parkinson’s disease It plays the role of cell protection and growth regulation in the process of myelin regeneration activated after toxic demyelination injury Inhibit macrophages, T lymphocytes, and their formation of interleukin and TNF-α, matrix metalloproteinases, and ROS Enhance cell cycle progression, mitosis, and cell survival, and inhibit neuronal apoptosis	[143,144,145,146,149,151,152]
Metallothionein	MT-III	Inhibition of neurite formation and survival of cortical neurons It has anti-Aβ activity and eliminates the toxic aggregates of Aβ peptide, so as to antagonize the neurotoxic effect of Aβ peptide It can effectively clear ROS and prevent neurite extension and differentiated cortical neuron death caused by exposure to high oxygen concentration	[153,154,155,159]