Effect of pesticides on phosphorylation of tau protein, and its influence on Alzheimer’s disease

Table 5 Effects of neonicotinoid pesticides on tau protein

Type of study	Sample	Type of pesticide	Exposure data	Tau phosphorylation	GSK-3β	PP2A	Other mechanisms	Ref.
Clinical/epidemiological studies. Clinical case	Accidental intake with Ns	Imidacloprid and thiamethoxam	Concentration: NA. Single dose	NA	NA	NA	The metabolite desnitro-imidacloprid activated the flow of intracellular calcium, thereby altering the response of kinase enzymes, and causing an excitatory neurological phase	[22]
Experimental studies	Primary cultures of cerebellar neurons from neonatal Sprague-Dawly rats	Acetamiprid imidacloprid	Concentrations: 1-100 μM. Exposure time of 600 s	NA	NA	NA	Exposure to Ns increased the influx of Ca2+ in cerebellar neurons. These pesticides excited cerebellar neurons to a degree similar to that from nicotine exposure. The influx of calcium ions activated the VDCC	[70]
Experimental studies	Human neural cells	Desnitro-imidacloprid	Concentration: 50 μM. Exposure time of 48 h	Increased	Increased	Decreased	Activation of Wnt signal pathway. Exposure induced tau hyperphosphorylation by a GSK-3β response, this enzyme is associated with Beta catenin activity. Exposure to this Ns induced watered-down expression that regulated tau hyperphosphorylation and apoptotic responses that impacted synaptotoxicity	[71]

Ns: Neonicotinoid; GSK-3β: Glycogen synthase kinase 3 beta; PP2A: Protein phosphatase-2A; NA: Not available; VDCC: Voltage-dependent calcium channels.