KEGG   NETWORK: N01199
Entry
N01199                      Network                                
Name
Scrapie conformation PrPSc to mGluR5-Ca2+ -apoptotic pathway
Definition
PRNP* -> (RYR,ITPR) -> Ca2+ -- MCU -> Ca2+(mito) -- MPTP -> CYCS == APAF1 -> CASP9 -> CASP3
  Expanded
5621v1 -> (6261,6262,6263,3708,3709,3710) -> C00076 -- 90550 -> C00076 -- (7416,7417,7419,291,292,293,83447) -> 54205 == 317 -> 842 -> 836
Class
nt06465 Prion disease
nt06466 Pathways of neurodegeneration
Type
Variant
Pathway
hsa05020  Prion disease
Disease
H00061  Prion disease
Gene
5621  PRNP; prion protein
6261  RYR1; ryanodine receptor 1
6262  RYR2; ryanodine receptor 2
6263  RYR3; ryanodine receptor 3
3708  ITPR1; inositol 1,4,5-trisphosphate receptor type 1
3709  ITPR2; inositol 1,4,5-trisphosphate receptor type 2
3710  ITPR3; inositol 1,4,5-trisphosphate receptor type 3
90550  MCU; mitochondrial calcium uniporter
7416  VDAC1; voltage dependent anion channel 1
7417  VDAC2; voltage dependent anion channel 2
7419  VDAC3; voltage dependent anion channel 3
291  SLC25A4; solute carrier family 25 member 4
292  SLC25A5; solute carrier family 25 member 5
293  SLC25A6; solute carrier family 25 member 6
83447  SLC25A31; solute carrier family 25 member 31
54205  CYCS; cytochrome c, somatic
317  APAF1; apoptotic peptidase activating factor 1
842  CASP9; caspase 9
836  CASP3; caspase 3
Variant
5621v1 (PRNP*)  PRNP scrapie conformation
Metabolite
C00076  Calcium cation
C00076  Calcium cation
Reference
  Authors
Ferreiro E, Oliveira CR, Pereira CM
  Title
The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway.
  Journal
Neurobiol Dis 30:331-42 (2008)
DOI:10.1016/j.nbd.2008.02.003
Reference
  Authors
Ferreiro E, Resende R, Costa R, Oliveira CR, Pereira CM
  Title
An endoplasmic-reticulum-specific apoptotic pathway is involved in prion and amyloid-beta peptides neurotoxicity.
  Journal
Neurobiol Dis 23:669-78 (2006)
DOI:10.1016/j.nbd.2006.05.011
Reference
  Authors
Torres M, Encina G, Soto C, Hetz C
  Title
Abnormal calcium homeostasis and protein folding stress at the ER: A common factor in familial and infectious prion disorders.
  Journal
Commun Integr Biol 4:258-61 (2011)
DOI:10.4161/cib.4.3.15019
Reference
  Authors
Hetz C, Mollereau B
  Title
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases.
  Journal
Nat Rev Neurosci 15:233-49 (2014)
DOI:10.1038/nrn3689
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