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

Table 1 Effect of organochlorine pesticides on tau protein

Type of study	Sample	Type of pesticide	Exposure data	Tau phosphory-lation	GSK-3β	PP2A	Other mechanisms	Ref.
Clinical/epidemiological studies. Cohort	13 postmortem brains of humans without exposure, and 4 postmortem brains of humans with exposure	OCs	Concentration: NA. Exposure time: From 0 to 10 yr	Increased	NA	NA	Exposure altered mitochondrial genes encoding MAPT and MAP1B. These are associated with MAPT phosphorylation and neurite formation that contributed to the development of tauopathies	[44]
Clinical/epidemiological studies. Cross-sectional	90 subjects with PD, and 90 healthy subjects	δ-HCH	Concentration: NA. Exposure time: NA	NA	NA	NA	Exposure was associated with MAPT rs16940758 polymorphism which was related to tau aggregation	[45]
Experimental studies	Strains of Caenorhabditis elegans (N2 BR5270)	DDT	Concentration: 3 μM. Exposure time of 2 h	Increased	NA	NA	DDT exacerbated tau protein toxicity, reduced mitochondrial respiration, and induced apoptosis	[42]
Experimental studies	Strains of Caenorhabditis elegans (N2 BR5271)	DDT	Concentration: 3 μM. Exposure time of 2 h	Increased	NA	NA	Exposure to DDT increased tau protein aggregation and modified mitochondrial respiration	[46]
Experimental studies	Female largemouth bass	Dieldrin	Concentration: 3.0 mg/kg. Exposure time of 57 d	NA	NA	Decreased	Increased expression of proteins in hypothalamus such as Snap25, Cytc, Eno1, Hba1, and H2bb. These proteins were elevated in the pathophysiology of mice with AD and were associated with tau protein. Additionally, downregulation of MAPT was observed, which affected phosphatase activity	[47]
Experimental studies	Wistar rats	Chlordane	Range of concentration: 1 to 100 nM. Chronic exposure	Not modified	NA	NA	No significant changes in tau protein levels from exposure to chlordane	[49]
Review studies	Multiple studies	TCDD	Range of concentration: 5-23 ppt. Single dose	Increased	Increased	NA	Increased intracellular calcium levels and tau phosphorylation in neurons through overexpression of GSK-3β and hence its enzymatic activity	[48]

OCs: Organochlorine; NA: Not available; MAPT: Microtubule associated protein tau; δ-HCH: δ-hexachlorocyclohexane; DDT: Dichlorodiphenyltrichloroethan; AD: Alzheimer’s disease; TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin; GSK-3β: Glycogen synthase kinase 3 beta; PD: Parkinson disease; ppt: Parts per thousand; PP2A: Protein phosphatase-2A.