References
(1) Nucleus and gene expression.  
Binding to DNA  
Binds to histone-DNA complex and induces conformational changes of chromatin. [20]
Induces topological changes of DNA. [21,22]
 
Altered gene expression.  
Induces decreased expression of neurofilament and tubulin. [23]
Induces altered expression of genes of neurofilament, APP, and neuron specific enolase. [24]
Induces decreased expression of transferrin receptor. [25]
Induces altered expression of RNA polymerase I. [26]
Induces downregulation of mitochondrial cytochrome c oxidase. [27]
Induces altered expression of calbindin-D28k. [28]
Induces decrease in the expression of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF). [29]
Induces expression of pro-inflammatory genes and pro-apoptotic genes. [30]
Induces elevated expression of APP. [31,32]
Induces altered expression of oxidative stress marker genes (SOD1, glutathione reductase, etc.). [33]
Induces decreased expression of neprilysin. [34]
Induces altered expression of β-APP secretase (BACE1 and BACE2). [35]
 
(2) Cellular functions  
Energy metabolismo  
Inhibits the activity of hexokinase [36]
Inhibits the activity of phosphofructokinase [37]
Inhibits the activity of glucose-6-phosphate dehydrogenase [38]
Causes mitochondrial dysfunction and depletion of ATP [39,40]
Decreases in activity and expression of TCA-cycle related enzymes (succinate dehydrogenase (SDH), alpha-ketoglutarate dehydrogenase (KGDH), isocitrate dehydrogenase-NAD+ IDH), fumarase (FUM), aconitase (ACN), and cytochrome c oxidase (Cyt C Ox)). [41]
 
Phosphorylation and dephosphorylation  
Inhibits the activity of protein phosphatase. [42]
Increases the activity of protein kinase C and cytoskeleton proteins. [43]
Accelerates phosphorylation and accumulation of neurofilament. [44]
Enhances Ca2+/Calmodulin dependent protein kinase activity. [45]
Accelerates phosphorylation of MAP 2 and neurofilament. [46]
Inhibits dephosphorylation of tau. [47]
Induces nonenzymatic phosphorylation of tau. [48]
 
Abnormal accumulation of proteins  
Causes the conformational change and the accumulation of neurofilament and MAP1A, MAP1B. [49]
Accelerates the phosphorylation of tau and its accumulation. [50]
Causes the accumulation of tau protein in neuroblastoma cells or in primary cultured neurons. [51,52]
Causes the accumulation of tau protein in experimental animals. [53,54]
Causes neurofibrillary degeneration in vivo. [55]
Causes the accumulation of AβP in cultured neurons or in neuroblastoma cells. [56,57]
Causes the accumulation of AβP in vivo. [58,59]
 
Neurotransmitter release  
Inhibits glutamate release. [60]
Impairs synaptic transmission. [61,62]
Inactivates glutamate dehydrogenase. [63]
Inhibits NMDA-type glutamate receptor. [64]
Inhibits choline acetyl transferase and tyrosine hydroxylase, glutamate decarboxylase. [65,66]
Influences acetyl-CoA and inhibits acetylcholine release. [67]
Activates monoamine oxidase. [68,69]
Inhibits dopamine beta-hydroxylase. [70]
Inhibits uptake of serotonin and noradrenalin in synaptosomes. [71]
 
Channel inhibition  
Influences the activities of Na+ channels and K+ channels. [72]
Enhances the voltage-activated Na+ channels. [73]
Inhibits the voltage-gated calcium channel. [62,74]
Inhibits the IP3-mediated Ca2+ release. [75]
 
Others  
Influences GTP binding proteins as aluminum fluoride. [76]
Inhibits GAP junction. [77]
Inhibits axonal transports. [78]
Binds to calmodulin and inhibition of calmodulin-binding enzymes. [79]
Induces inflammatory responses. [80]
 
(3) Membrane lipids  
 
Peroxidation  
Accelerates iron-induced membrane lipid peroxidation. [81]
Enhances lipid peroxidation in liposomes. [82]
Induces peroxidation of myelin lipids in vivo. [83]
Increases peroxidation products (malondialdehyde). [50]
 
Membrane properties  
Causes the change the lipid/phospholipids profiles of myelinin vivo. [84]
Induces the change in membrane physical properties (surface potential, lipid fluidity, and lipid arrangement). [83]
Induces the change of membrane fluidity. [85]
 
(4) Higher functions  
 
Cell death  
Causes the apoptotic neuronal death. [86,87]
Causes the apoptosis of astrocytes. [88]
Causes the death of motor neuron. [89,90]
 
Behavior, learning, and memory, others  
Inhibits long term potentiation (LTP). [91,92]
Causes learning disorder or memory deficit in experimental animals. [93–95]
Influences electrical activity in hippocampus and inhibits spatial learning memory deficit in aging rats. [96]
Causes memory deficit in AD model mice. [97,98]
Causes encephalopathy in dialysis patients. [99]
Causes encephalopathy in patients with renal failure. [100]
Table 1: Effects of aluminum on the development of the central nervous system.
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