KEGG   NETWORK: N00985
Entry
N00985                      Network                                

Name
Mutation-caused aberrant Htt to mGluR5-Ca2+ -apoptotic pathway
Definition
Glutamate -> GRM5 -> GNAQ -> PLCB -> IP3 -> (ITPR+HTT*) -> Ca2+ -- MCU -> Ca2+(mito) -- MPTP -> CYCS -- APAF1 -> CASP9 -> (CASP3,CASP7)
  Expanded
C00025 -> 2915 -> 2776 -> (23236,5330,5331,5332) -> C01245 -> ((3708,3709,3710)+3064v1) -> C00076 -- 90550 -> C00076 -- (7416,7417,7419,291,292,293,83447) -> 54205 -- 317 -> 842 -> (836,840)
Class
nt06410 Calcium signaling
nt06461 Huntington disease
Type
Variant
Pathway
hsa05016  Huntington disease
Disease
H00059  Huntington disease
Gene
2915  GRM5; glutamate metabotropic receptor 5
2776  GNAQ; G protein subunit alpha q
23236  PLCB1; phospholipase C beta 1
5330  PLCB2; phospholipase C beta 2
5331  PLCB3; phospholipase C beta 3
5332  PLCB4; phospholipase C beta 4
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
3064  HTT; huntingtin
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
840  CASP7; caspase 7
Variant
3064v1 (HTT*)  HTT mutation
Metabolite
C00025  L-Glutamate
C01245  D-myo-Inositol 1,4,5-trisphosphate
C00076  Calcium cation
C00076  Calcium cation
Reference
  Authors
Bezprozvanny I, Hayden MR
  Title
Deranged neuronal calcium signaling and Huntington disease.
  Journal
Biochem Biophys Res Commun 322:1310-7 (2004)
DOI:10.1016/j.bbrc.2004.08.035
Reference
  Authors
Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I
  Title
Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease.
  Journal
Proc Natl Acad Sci U S A 102:2602-7 (2005)
DOI:10.1073/pnas.0409402102
Reference
  Authors
Mackay JP, Nassrallah WB, Raymond LA
  Title
Cause or compensation?-Altered neuronal Ca(2+) handling in Huntington's disease.
  Journal
CNS Neurosci Ther 24:301-310 (2018)
DOI:10.1111/cns.12817
Reference
  Authors
Ureshino RP, Erustes AG, Bassani TB, Wachilewski P, Guarache GC, Nascimento AC, Costa AJ, Smaili SS, Pereira GJDS
  Title
The Interplay between Ca(2+) Signaling Pathways and Neurodegeneration.
  Journal
Int J Mol Sci 20:E6004 (2019)
DOI:10.3390/ijms20236004
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