Table 3.

Effects of neurotoxic agents on iGluRs and mGluRs in the onset and progression of Alzheimer’s disease.

SL	Neurotoxic agents	Study type	Molecular targets	Key modulating effects	References
Excitatory amino acids
1	BMAA	In vitro In vivo	AMPAR/KAR, NMDAR, mGluR5	Neuroinflammation, oxidative stress, apoptosis, cognitive impairment	[129]
2	Glutamate	In vitro In vivo	iGluR and mGluR	Induction of apoptosis, autophagy mitochondrial dysfunction, oxidative damage and neuroinflammation.	[130,131,132,25]
3	Homocysteine	In vivo	NMDAR, mGluR1	Synaptic dysfunction, oxidative stress, neurochemical imbalance, apoptosis/necrosis, neuronal cell death	[133,134]
Excitatory amino acid agonist
1	Domoic acid (DomA)	In vivo	iGLuR	Neuroinflammation, mitochondrial dysfunction, production of ROS	[135]
2	Kainic acid	In vitro In vivo	iGluR	Production of ROS, mitochondrial dysfunction, neuroinflammation and neuronal autophagy	[136]
CNS stimulant
1	Harmaline	In-vivo	NMDARs, AMPARs and mGluR1	Disturbance in motor function, production of tremors	[137]
Industrial organic compound
1	Bisphenol-A	In vitro	NMDAR, AMPAR	Production of neurotoxicity	[138,139,139]
Inorganic compound
1	Ammonia	In vivo	NMDAR	Reduction of glutamine synthetase activity, decreased elimination of ammonia from the brain	[140]
2	Hydrogen peroxide	In vitro	NMDAR	Alteration in synaptic transmission, oxidative stress, mitochondrial dysfunction, cytotoxicity, apoptosis, neuronal cell death	[141]
3	Mercury	In vitro	NMDAR	Mitochondrial dysfunction, oxidative stress, neuroinflammation, apoptosis, neuronal cell death	[28,142,143]
4	Sodium azide	In vitro	NMDAR	Mitochondrial dysfunction, oxidative stress, neuroinflammation, neuronal cell death	[144]