Parkinson’s Disease

Review Article

The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease

Table 1

Nrf2 target genes.


Group	Gene symbol	Gene name	Function

	GSH	γ-glutamyl-cysteinyl-glycine	Maintains redox homeostasis during oxidative stress
	GST	Glutathione-S-transferase	Cellular detoxification
	Gcl	Glutamate cysteine ligase	Catalyzes glutathione synthesis
Glutathione homeostasis	Gcs	Glutamate cysteine synthetase	Catalyzes glutathione synthesis
	GS	Glutathione synthetase	Catalyzes glutathione synthesis
	GPx	Glutathione Peroxidase	Catalyzes reduction of H₂O₂ or organic hyperoxides to water
	GR	Glutathione Reductase	Catalyzes reduction of oxidized GSSH to GSH

	NQO-1	NAD(P)H quinone oxidoreductase-1	Catalyzes two-electron reduction of quinones
Drug metabolism	Ugt	UDP-glucuronosyltransferases	Catalyzes endogenous and exogenous substances with glucuronic acid
	mEH	Microsomal epoxide hydrolase	Inactivates epoxides converting to vicinal dihydrodiol

Stress response proteins/iron metabolism	Ferritin	Ferritin	Iron binding protein having role in iron oxidative stress
Stress response proteins/iron metabolism	HO-1	Heme oxygenase-1	Catalyzes oxidative cleavage of Fe-protoporphyrin-IX

Excretion/transporter	Mdr	Multi-drug resistance protein	Drug efflux pump for xenobiotic compounds
Excretion/transporter	Mrp	Multidrug resistance associated protein	Multispecific organic anion transporter

	G6PDH	Glucose-6-phosphate dehydrogenase^a	Glycolysis
Other genes metabolism	Taldo	Transaldolase^a	Pentose phosphate pathway enzyme
	Tkt	Transketolase^a	Channeling of excess glucose phosphates to glycolysis

	Pafah	PAF acetylhydrolase^a	Catalyzes the degradation of platelet-activating factor to biologically inactive products
Immune system	Ptgs2	Prostaglandin-endoperoxide synthase 2^a	Prostaglandin biosynthesis
Immune system	Dig	Dithiolethione-inducible gene^a	Inhibition of chemically induced tumorigenesis
	Tac2	Tachykinin 2^a	Peptide neurotransmitter

	Calb1	Calbindin-28K^b	Calcium binding protein
Calcium homeostasis	Syt1	Synaptotagmin-1^b	Synaptic transmission
Calcium homeostasis	Hpca	Hippocalcin^b	Calcium binding protein
	S100A1	S100 calcium binding protein A1^b	Calcium binding protein

	Ngfg	Nerve growth factor-γ ^b	Growth factor for neuron survival
Growth factor	FGF-13	Fibroblast growth factor-13^b	Nervous system development and function
Growth factor	FGF-14	Fibroblast growth factor-14^b	Nervous system development and function
	BDNF	Brain-derived neurotrophic factor^b	Growth factor for neuron survival

	nGEF	Neuronal GEF^b	Intracellular signaling networks
	Prkcb	Protein Kinase C-β ^b	Signal transduction
Intracellular signaling	Gng3	G-protein-γ3^b	Signal transduction
	Adm	Adrenomedullin^b	Adrenal development
	Crh	Corticotropin-releasing hormone^b	Hormone released in response to stress

Neurotransmission/channel	Clcn	Chloride channel^b	Ion channel protein
	Gabr1	GABA-A receptor-1^b	Neurotransmitter receptor
	Gabrg3	GABA-A receptor, gamma 3^b	Neurotransmitter receptor
	Gabbr1	GABA-B receptor-1^b	Neurotransmitter receptor

Nrf2 activates a battery of ARE-driven genes, also known as classic Nrf2-target genes, which are classified into 4 groups as glutathione homeostasis, drug metabolism, stress-response protein/iron metabolism, and excretion/transporter [43]. In addition to classic genes, microarray experiments revealed cell-type specific target genes. From (a) primary astrocyte and (b) primary neuronal cultures, novel targets were identified [44]. They also are stated as other genes.