Table 5 A list of differentially expressed proteins in the cerebellum with fundamental roles in the regulation of cell death

F1LMM8

Q64536

Pdk2

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

–

↓ (0.41)

–

–

–

p53 activation decreases Pdk2 transcription [92]

P97570

Pla2g6

85/88 kDa calcium independent phospholipase A2

S

–

N

M

M

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]

Q9JKL8

Adnp

Activity-dependent neuroprotector homeobox protein

–

–

C

–

M

Down-regulation of Adnp up-regulates p53 [144]

NAP sequence of Adnp reduces activity of caspase-3 [145]

Dysregulation of Adnp expression increases Bcl-2 expression in hippocampus [146]

G3V8Q9

A0A0G2K8G0

P70478

Apc

Adenomatosis polyposis coli

–

C

N

M

N

APC can regulate apoptosis by governing the level of caspase-3 [134]

P23928

Cryab

Alpha-crystallin B chain

S

↓ (0.50)

–

–

–

Cryab prevents apoptosis; it binds to caspase-3 [134], Bax and Bcl-X_S [135] and p53 [136]

Cryab gene is a targer of p53 and p53-dependent apoptosis is affected by Cryab expression [136]

A0A0G2JZS5

Q7TS62

P53563

E9PU78

Bcl2l1

Bcl-2-like protein 1

–

–

N

M

M

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

–

N

M

M

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

A0A0G2JSK3

Q8CH27

Rcan2

Calcipressin-2

S

–

N

M

M

Calcineurin regulation [138]

F1LS29

P97571

Capn1

Calpain-1 catalytic subunit

N

S

N

N

M

Calpain is a Ca²⁺-dependent protease, which cleaves Bid, Bcl-2, Bcl-X_L [17] and Bax [80]

It cleaves caspase-3, -8 and -12, p53 and NMDA receptors [81]

A0A0G2JYD8

G3V7U6

Q8R4C0

Capn5

Calpain-5

–

S

N

N

M

Ca²⁺-dependent protease

P55213

Casp3

Caspase-3

–

N

S

N

F

Cleavage 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

S

N

F

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]

P15337

A0A0G2K748

Creb1

Cyclic AMP-responsive element-binding protein 1

–

C

C

–

N

Enhanced Creb activity leads to increased Bcl-2 promoter activity and cell survival [147]

F1MAJ0

A0A0G2JY48

Ephb2

Eph receptor B2

-

S

–

F

–

Ephb2 can prevent against Fas-triggered apotosis by inhibition of caspase-8 and caspase-3 [140]

Q8R2E7

Fadd

FAS-associated death domain protein

–

C

–

–

F

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

Overexpression of FADD promotes apoptosis [103]

Q63226

F1LXB6

Grid2

Glutamate ionotropic receptor, delta-2

–

↑ (3.12)

–

–

–

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

–

S

–

F

–

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

Q62648

P35439

Grin1

Glutamate ionotropic receptor, NMDA 1

–

C

–

–

F

Up-regulation of Grin1 (NR1 subunit) is associated with increased expression of Bax and decreased expression of Bcl-X_L [148]

Q00959

G3V9C5

Grin2a

Glutamate ionotropic receptor, NMDA 2A

S

S

N

N

M

NMDARs containing Grin2a (NR2A subunit) promotes neuronal survival [149]; down-regulation of Creb was exaggerated in neurons over-expressing Grin2A [83]

G3V746

Q00960

Grin2b

Glutamate ionotropic receptor, NMDA 2B

C

S

N

N

M

NMDARs containing Gin2b (NR2B subunit) promotes neuronal death [149]; down-regulation of Creb was exaggerated in neurons over-expressing Grin2b [83]

A0A0G2JSH8

Q00961

Grin2c

Glutamate ionotropic receptor, NMDA 2C

S

S

S

N

–

NR2C expression supports neuronal survival [150]

O35821

Mybbp1a

Myb-binding protein 1A

–

–

C

–

M

Mybbp1a can increase Bax expression via p53 acetylation [151]

Mybbp1a down-regulation induces apoptosis via caspase-3 activation [152]

P06907

Mpz

Myelin protein P0

C

↓ (0.34)

↑ (4.08)

↑ (7.98)

–

Mpz knockdown induced apoptosis [114]

A0A0G2JZT0

Q64663

P2rx7

P2X purinoceptor 7

S

–

–

–

–

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

–

N

↑ (3.97)

F

F

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]

P70600

Ptk2b

Protein-tyrosine kinase2-beta

C

C

C

↑ (5.55)

N

Overexpression of Ptk2b can induce apoptosis [143]

D4ADQ1

Rrm2b

Ribonucleotide reductase M2 B (TP53 inducible)

N

N

C

F

N

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

–

S

–

F

–

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]

D4A280

Pak7

Serine/threonine-protein kinase PAK 5

–

S

C

F

M

Pak7 expression can prevent apoptosis by phosphorylating of Bad on Ser112 and inhibition of caspase-3 and PARP cleavage [153]

D4A9G3

A0A0G2K2P3

Tnfaip8

TNF-α induced protein 8

C

C

C

–

N

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