Table 3 A list of differentially expressed proteins in the prefrontal cortex with fundamental roles in the regulation of cell death

F1LMM8

Q64536

Pdk2

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

–

↓ (0.35)

–

–

–

p53 activation decreases Pdk2 transcription [92]

P97570

Pla2g6

85/88 kDa calcium independent phospholipase A2

S

–

–

–

–

tBID and Bax augments Pla2g6 (iPLA2) activity via ROS production leading to changes in the MOM [93]

Overexpression of iPLA2 increased the rate of apoptosis, iPLA2 is cleaved by caspase-3 [94]

β-cell apoptosis is attributable to the modulation of 5′SS selection in Bcl-X pre-mRNA by bioactive lipids modulated by iPLA2 [95]

G3V8T9

Q9JKL3

Q63690

Bax

Apoptosis regulator BAX

–

N

C

F

–

Pro-apoptotic member of Bcl-2 family, its activation permeabilizes the MOM during apoptosis [96]

Deletion of Bax is sufficient to inhibit apoptosis [97]

Bax is cleaved by active calpains [80]

A0A0G2JZS5

Q7TS62

P53563

E9PU78

Bcl2l1

Bcl-2-like protein 1

C

–

–

–

–

Bcl2l1 (Bcl-X) gene generates two protein products by alternative pre-mRNA splicing: Bcl-X_L is anti-apoptotic, while Bcl-X_S is pro-apoptotic; deletion of Bcl-X in mice results in neuronal death in the brain during late embryonic development; Bcl-X_L overexpression attenuates brain injury in neonatal rodents [77]

Q91XJ1

Becn1

Beclin-1

–

N

C

F

N

Beclin-1-induced autophagy is inversely correlated with apoptosis [13]

Q6IN33

Rcan1

Calcipressin-1

C

N

C

F

N

Calcineurin regulation; Rcan1 absence enhances calcineurin activity and Fas ligand expression [98]

F1LPH1

P27321

D3ZL24

Cast

Calpastatin

S

N

S

N

F

Cast is a specific endogenous inhibitor of calpains and is cleaved by caspases [99]

P55213

Casp3

Caspase-3

–

S

C

F

M

Ceavage and activation of caspase-3 initiates apoptosis; essential for neuronal cell death [100]

Caspase-3 expression is regulated with age [21]

A regulatory calpain/caspase-3 cross-talk [101]

Q1HL14

Cers1

Ceramide synthase 1

–

S

N

N

M

Inhibition of de novo ceramide synthesis inhibited caspase 3/7 activation and apoptosis [102]

Overexpression of CerS1 and increased level of C18 ceramide resulted in activation of ER stress and inhibition of cell viability, independent of Bax [103]

Q5RK17

D4A7Z5

Diablo LOC100360940

Diablo homolog

S

C

–

–

F

Diablo is located in the intermembrane space of mitochondria and is released into the cytosol during apoptosis and thereby enabling the activation of caspases [104]

Q8R2E7

Fadd

FAS-associated death domain protein

–

S

S

N

–

Pro-apoptotic adapter protein involved in extrinsic pathway of apoptosis [100]

Overexpression of FADD promotes apoptosis [104]

Q63226

F1LXB6

Grid2

Glutamate ionotropic receptor, delta-2

C

C

C

↓ (0.47)

–

Gain-to-function mutation of Grid2 induces neuronal death [105]; this mutation is associated with increased expression of Bax, Bcl-X_S, caspase-3 and -8 [106]

TNF-α has a role in regulation of Grid2 gene expression, which can be a suppressor in TNF-induced neurodegeneration [107]

P42260

F1M855

Grik2

Glutamate ionotropic receptor, kainate 2

N

S

–

F

–

Grik2 (GluR6) promotes Bax translocation and increase in caspase-3 activation [108]

Q8VH49

Higd1a

HIG1 domain family 1A, mitochondrial

S

S

N

N

M

Higd1a is a survival factor and is associated with caspase-3 activation [109, 110]

F1MAL5

Irs2

Insulin receptor substrate 2

N

C

N

M

N

CaMK4/CREB/IRS2 cascade can inhibit apoptosis [111]

IRS2 knockout increased cell death and activation of caspase-3 and -8 as well as the levels of Fadd, Bcl-2, Bcl-X_L and p53 [112]

P31423

Grm4

Metabotropic glutamate receptor 4

–

C

C

–

N

Decreased expression of GRM4 gene is associated with apoptosis of cerebellar granule neurons [86]

Activation of Grm4 can activate pro-caspase 8/9/3 and disrupt the balance of Bcl-2/Bax expression [113]

P06907

Mpz

Myelin protein P0

N

C

N

M

N

Mpz knockdown induced apoptosis [114]

A0A0G2JZT0

Q64663

P2rx7

P2X purinoceptor 7

S

↓ (0.39)

–

↑ (3.28)

–

P2rx7s mediate caspase-8 and caspase-3 dependent apoptosis [115]

Its activation is associated with Ca²⁺ responses and TNF-α production [116,117,118]

F1LNG8

Q5BK62

Mpv17

Protein Mpv17

S

C

C

–

N

The increase of Mpv17 expression can be accompanied by the enhanced expression of p53, Bax, cyt c and active caspase-3 and decreased expression of Bcl-2 in the pathological proces [119]

B1WC67

Slc25a24

RCG29001

–

–

S

–

F

A survival factor, knock-down of Slc25a24 led to reduction of Ca²⁺ buffering capacity and sensitized cellts to cell death induced by mitochondrial permeability transition [120]

Q63259

Ptprn

Receptor–type tyrosine protein phosphatase-like N

–

–

C

–

M

Ptprn knock-down can prevent apoptosis [121]

Q63639

Aldh1a2

Retinal dehydrogenase 2

N

–

–

↓ (0.36)

–

Aldh1a2 mediates conversion of retinol into active retinoic acid altering the expression of Bcl-2, Bax, Bid, caspase-8 and -3 [122]

D4ADQ1

Rrm2b

Ribonucleotide reductase M2 B (TP53 inducible)

N

S

C

F

M

Loss of Rrm2b can increase apoptosis [123]

Rrm2b expression is induced by stress [124]

Rrm2b cleavage is mediated by caspase-8 and -3 [125]

P70501

A0A0G2K3S6

Rbm10

RNA-binding protein 10

C

S

C

F

M

Rbm10 knock-down can decrease caspase activation [126]

Rbm10 regulates alternative splicing of Fas and Bcl-X genes [127]

Rbm10 expression is associated with increased apoptosis [128]

A0A0G2JXI4

P52632

Stat5b;Stat5a

Signal transducer and activator of transcription

S

S

N

N

M

Stat5 regulate expression of Bcl-2 and Bcl-X_L and the level of caspase-3 [129,130,131]

D4A9G3

A0A0G2K2P3

Tnfaip8

TNF-α induced protein 8

N

S

–

F

–

Tnfaip8 can suppress TNF-mediated apoptosis by inhibiting TNF-induced caspase-8 activity [69]

F1M5H6

D4A6A8

A0A0G2KB61

Tp53bp2

Tumor protein p53-binding protein 2

S

S

–

F

–

Tp53bp2 binds to p53 and Bcl-2; it can alter p53 protein conformation and enhance the binding activity of p53 to the promotes of Bax [132]