1. E
E
E
E
E E
E
E
E
E
E
E E
E
E
NOS1
CaMCaM
Arg
NO
sGC
MC
NMDAr
Neuron

2. NOS2
Arg
NO
sGC
MC
Pro-inflammatory stimuli
Astrocytes

3. Blood
Vessel
VGEF-A
VEFGR-2
NOS3
eNOS
NONO
VSMC
relaxation
Vaso-
dilation
sGC 5’ GMP
cGMP
cGMP-gated
ion channels
Na+
Ca2+
NO
sGC
cGMP
5’ GMP
cGMP-gated
ion channels
Na+
Ca2+

4. C
NOS1
Arg•NOO
2
• −
C
C
C
C
C
C
ETC
ONOO−
SOD
H2O2
•OH
Fe2+
Fe3+
GPxGSR
H2O
GSH
GSSG
Neuron
Formation and elimination of ROS and RNS in neurons

5. Astrocytes co-operate with neurons for antioxidant GSH biosynthesis
Cul3
GCL
Nrf2
Keap1
Nrf2
GSH
GlnGln
GSH
CysGlyCysGly
X
γGluX
Glu
γGluCys
GCL
GS
GSH
Neuron Astrocyte

6. Neuronal glucose metabolism supports antioxidant GSH
Glucose
G6P
F6P
6PG
R5P
NADP+
NADPH GSSG
GSH
F1,6P2
Pyr
NAD +
NADH
ADP
ATP
Pfk1
Pfkfb3
APC/C
Cdh1
F2,6P2
+
G6PD
NADPH
NADP+
GSSG
GSH

7. K
K
Astrocytes and neurons
couple glucose metabolism to antioxidant defense
Neuron Astrocyte
C
C
C
C C
Glucose
G6P
R5P
G6P
Pyr
Pyr
NADPH
NADP+
GSSG
GSH
ROS Nrf2
GSH
NAD+ NADH
Lac
APC/C
Cdh
1
ATP
CO2
s
s
s
K
K
s
s
s
ATP
ADP