Table 4.

L-BMAA treatment in different experimental models.

Experimental Model	L-BMAA Exposure Protocol	Molecular Target	Reference
SH-SY5Y	3 mM plus antagonist for kainate/AMPA receptors 5 days	low neurotoxicity of BMAA and weak action at glutamatergic receptors	[135]
	0.1 mM 48h	Low non-excitotoxic BMAA concentrations induce effects on the ubiquitin/proteasome system not ROS-related	[129]
	3–10 mM 48h	decrease cell viability in a dose-response manner and evoke alterations in GSK3β and TDP-43	[136]
	0.5 mM 24h–48h–72h	Increased caspase-3 activity and cathepsins, ER stress	[137]
	0.05–0.25–1 mM 24 h	alterations in alanine, aspartate, and glutamate metabolism	[138]
	0.1–1 mM 24–48 h	autophagy	[139]
	3 mM 48h	disrupts mitochondrial metabolism	[140]
PC12	2 mM 6–12 h	apoptosis and mGluR1 increase	[141]
	0.4–1 mM 48h	promoted cell death and axon-like outgrowth	[142]
NSC-34	0.1–1 mM 72 h	exposure to BMAA causes protein misfolding, ER stress, induction of the UPR, disruption of the mitochondrial function	[130,141]
NIH/3T3	1–3 mM 48–96 h	L-BMAA causes arrest of cell cycle progression at the G1/S. No evidence of cell membrane damage, apoptosis, or ROS overproduction	[143]
primary cortical neurons	3 mM 1 h 20 mM HCO3-	L-BMAA activity is dependent on HCO3-, resulting in a destruction of cortical neuronal population.	[115] [144]
primary cerebellar granule cells colture, rat	up to 3 mM 24–48h	L-BMAA induced both necrotic- and apoptotic-like cell death	[145]
primary neurons and astrocytes cortical cell cultures, fetal mouse	3–10 mM 3–24h 0.1 mM 48h	enhancement death of cortical neurons damaged by other insults; oxidative stress, Wallerian-Like Degeneration	[146,147,148]
neural stem cells	50  µM–3  mM 24 h	apoptosis, cellular differentiation, neurite outgrowth, and DNA methylation	[133]