General Information:

Id: 172
Diseases: Amyotrophic lateral sclerosis
Mus musculus
SOD1(G93A) fast-mice
BTO:0000312 motoneuron (vulnerable)
article
Reference: Saxena S et al.(2009) A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice Nat. Neurosci. 12: 627-636 [PMID: 19330001]

Interaction Information:

Comment From stage P12 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of genes involved in stress-related pathways, including protein ubiquitination, hypoxia and NRF2-mediated stress pathways. This stress-related response increased up to P26 but was abruptly lost at P32 and beyond.
Formal Description
Interaction-ID: 691

gene/protein mutant

SOD1-p.G93A

increases_activity of

in motoneurons; from stage P12 up to P26
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 696

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

EIF2A

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 701

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

ATF4

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 702

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

GADD45A

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 703

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

ATF3

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 704

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

LAPTM5

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 707

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

GRN

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 708

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

NRN1

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 709

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

HEXB

in motoneurons; from stage P32 on
Drugbank entries Show/Hide entries for HEXB
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed an upregulation of unfolded protein response (UPR)-related genes: Eif2a, Atf4, Gadd45, Atf3, Laptm5, Grn, Nrn1, Hexb and Perk.
Formal Description
Interaction-ID: 710

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

EIF2AK3

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed downregulation of UPS (ubiquitin proteasome system) related genes: Usp53, Uchl5 and Ube2q.
Formal Description
Interaction-ID: 711

gene/protein mutant

SOD1-p.G93A

decreases_expression of

gene/protein

USP53

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed downregulation of UPS (ubiquitin proteasome system) related genes: Usp53, Uchl5 and Ube2q.
Formal Description
Interaction-ID: 712

gene/protein mutant

SOD1-p.G93A

decreases_expression of

gene/protein

UCHL5

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed downregulation of UPS (ubiquitin proteasome system) related genes: Usp53, Uchl5 and Ube2q.
Formal Description
Interaction-ID: 713

gene/protein mutant

SOD1-p.G93A

decreases_expression of

gene/protein

UBE2Q1

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed upregulation of microglial responsive genes: Ifih1, Ifitm3 and C1qb.
Formal Description
Interaction-ID: 716

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

IFIH1

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed upregulation of microglial responsive genes: Ifih1, Ifitm3 and C1qb.
Formal Description
Interaction-ID: 717

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

IFITM3

in motoneurons; from stage P32 on
Comment From stage P32 on, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice specifically showed upregulation of microglial responsive genes: Ifih1, Ifitm3 and C1qb.
Formal Description
Interaction-ID: 718

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

C1QB

in motoneurons; from stage P32 on
Drugbank entries Show/Hide entries for C1QB
Comment From stage P20 to P38, VUL but not RES motoneurons (VUL=vulnerable to motoneuron disease, RES=resistant to) of G93A-fast mice showed increased expression ofthe ER stress marker protein BiP.
Formal Description
Interaction-ID: 737

gene/protein mutant

SOD1-p.G93A

increases_expression of

gene/protein

HSPA5

in motoneurons; from stage P20 to P38
Drugbank entries Show/Hide entries for HSPA5
Comment Early salubrinal treatment led to low levels of BiP, no evidence of a UPR and no microglial activation at stage P38 and to early signs of a UPR, mild microglial activation and no loss of synaptic vesicles at neuromuscular junctions at stage P53 in mutant SOD1-G93A-fast mice (VUL) motoneurons.
Formal Description
Interaction-ID: 746

drug/chemical compound

Salubrinal

decreases_activity of

in mutant SOD1-G93A-fast mice
Comment The stress-protecting factor CNTF effectively attenuated the axonal pathology in VUL motoneurons in mutant G93A-fast-mice.
Formal Description
Interaction-ID: 747

gene/protein

CNTF

decreases_activity of

in mutant SOD1-G93A-fast mice
Comment Early salubrinal treatment led to low levels of BiP, no evidence of a UPR and no microglial activation at stage P38 and to early signs of a UPR, mild microglial activation and no loss of synaptic vesicles at neuromuscular junctions at stage P53 in mutant SOD1-G93A-fast mice (VUL) motoneurons.
Formal Description
Interaction-ID: 757

drug/chemical compound

Salubrinal

decreases_expression of

gene/protein

HSPA5

in motoneurons; in mutant SOD1-G93A-fast
Drugbank entries Show/Hide entries for HSPA5
Comment The stress-protecting factor CNTF prevented the upregulation of BiP in VUL motoneurons in mutant G93A-fast-mice.
Formal Description
Interaction-ID: 770

gene/protein

CNTF

decreases_expression of

gene/protein

HSPA5

in motoneurons; in mutant SOD1-G93A-fast mice
Drugbank entries Show/Hide entries for HSPA5
Comment Early salubrinal treatment led to low levels of BiP, no evidence of a UPR and no microglial activation at stage P38 and to early signs of a UPR, mild microglial activation and no loss of synaptic vesicles at neuromuscular junctions at stage P53 in mutant SOD1-G93A-fast mice (VUL) motoneurons.
Formal Description
Interaction-ID: 51037

drug/chemical compound

Salubrinal

decreases_expression of

gene/protein

HSPA5

in motoneurons; in mutant SOD1-G93A-fast mice
Drugbank entries Show/Hide entries for HSPA5