Entry Name Spinocerebellar ataxia - Ursus arctos (brown bear)
Description The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. Compelling evidence points to major aetiological roles for transcriptional dysregulation, protein aggregation and clearance, autophagy, the ubiquitin-proteasome system, alterations of calcium homeostasis, mitochondria defects, toxic RNA gain-of-function mechanisms and eventual cell death with apoptotic features of neurons during SCA disease progression.
Class Human Diseases; Neurodegenerative diseaseBRITE hierarchy
Pathway map Ortholog table Organism Ursus arctos (brown bear) [GN:
uah ]
Gene 113255631 TRPC3; short transient receptor potential channel 3 isoform X3 [KO:K04966 ]
113269831 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
113242038 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
113247199 CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344 ]
113257782 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
113243814 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
113248424 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X3 [KO:K05208 ]
113244660 GRIN2C; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C [KO:K05211 ]
113260377 GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213 ]
113259163 MCU; calcium uniporter protein, mitochondrial isoform X1 [KO:K20858 ]
113261734 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
113259206 VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
113245581 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
113254614 OMA1; metalloendopeptidase OMA1, mitochondrial isoform X1 [KO:K23010 ] [EC:3.4.24.-]
113244052 SPTBN2; spectrin beta chain, non-erythrocytic 2 isoform X3 [KO:K23932 ]
113264959 PSMC3; 26S proteasome regulatory subunit 6A isoform X2 [KO:K03065 ]
113265286 PSMC5; 26S proteasome regulatory subunit 8 isoform X1 [KO:K03066 ]
113254324 PSMD2; 26S proteasome non-ATPase regulatory subunit 2 [KO:K03028 ]
113250358 PSMD1; 26S proteasome non-ATPase regulatory subunit 1 isoform X1 [KO:K03032 ]
113265502 PSMD3; 26S proteasome non-ATPase regulatory subunit 3 isoform X2 [KO:K03033 ]
113266933 PSMD9; 26S proteasome non-ATPase regulatory subunit 9 [KO:K06693 ]
113265256 PSMD12; 26S proteasome non-ATPase regulatory subunit 12 [KO:K03035 ]
113268987 PSMD11; 26S proteasome non-ATPase regulatory subunit 11 isoform X1 [KO:K03036 ]
113257041 PSMD6; 26S proteasome non-ATPase regulatory subunit 6 [KO:K03037 ]
113247228 LOW QUALITY PROTEIN: 26S proteasome non-ATPase regulatory subunit 6-like [KO:K03037 ]
113252438 PSMD7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038 ]
113248771 PSMD13; 26S proteasome non-ATPase regulatory subunit 13 isoform X1 [KO:K03039 ]
113246142 PSMD4; 26S proteasome non-ATPase regulatory subunit 4 isoform X2 [KO:K03029 ]
113243618 PSMD8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031 ]
113265667 ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 isoform X1 [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
125281549 SLC1A6; excitatory amino acid transporter 4 isoform X1 [KO:K05617 ]
113258648 RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053 ]
113266766 RBPJ; recombining binding protein suppressor of hairless isoform X4 [KO:K06053 ]
113261320 NFYA; nuclear transcription factor Y subunit alpha isoform X1 [KO:K08064 ]
113268105 RB1CC1; RB1-inducible coiled-coil protein 1 isoform X1 [KO:K17589 ]
113264983 AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform X1 [KO:K17985 ]
113242341 ATG14; beclin 1-associated autophagy-related key regulator [KO:K17889 ]
113244147 ATG2A; autophagy-related protein 2 homolog A isoform X3 [KO:K17906 ]
113267295 ATG2B; autophagy-related protein 2 homolog B isoform X1 [KO:K17906 ]
113267967 WIPI2; WD repeat domain phosphoinositide-interacting protein 2 isoform X1 [KO:K17908 ]
113265240 WIPI1; WD repeat domain phosphoinositide-interacting protein 1 isoform X1 [KO:K17908 ]
113247246 KCNC3; potassium voltage-gated channel subfamily C member 3 isoform X1 [KO:K04889 ]
113244424 KCND3; potassium voltage-gated channel subfamily D member 3 [KO:K04893 ]
113270178 VLDLR; very low-density lipoprotein receptor isoform X2 [KO:K20053 ]
113254799 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113270537 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113253989 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113256705 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113254730 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649 ]
113255266 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
Reference Authors Matilla-Duenas A, Sanchez I, Corral-Juan M, Davalos A, Alvarez R, Latorre P
Title Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias.
Journal Reference Authors Duenas AM, Goold R, Giunti P
Title Molecular pathogenesis of spinocerebellar ataxias.
Journal Reference Authors Mark MD, Schwitalla JC, Groemmke M, Herlitze S
Title Keeping Our Calcium in Balance to Maintain Our Balance.
Journal Reference Authors Egorova PA, Bezprozvanny IB
Title Inositol 1,4,5-trisphosphate receptors and neurodegenerative disorders.
Journal Reference Authors Shimobayashi E, Kapfhammer JP
Title Calcium Signaling, PKC Gamma, IP3R1 and CAR8 Link Spinocerebellar Ataxias and Purkinje Cell Dendritic Development.
Journal Reference Authors Kasumu A, Bezprozvanny I
Title Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias.
Journal Reference Authors Egorova P, Popugaeva E, Bezprozvanny I
Title Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.
Journal Reference Authors Hisatsune C, Hamada K, Mikoshiba K
Title Ca(2+) signaling and spinocerebellar ataxia.
Journal Reference Authors Takada SH, Ikebara JM, de Sousa E, Cardoso DS, Resende RR, Ulrich H, Ruckl M, Rudiger S, Kihara AH
Title Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.
Journal Reference Authors Brown SA, Loew LM
Title Integration of modeling with experimental and clinical findings synthesizes and refines the central role of inositol 1,4,5-trisphosphate receptor 1 in spinocerebellar ataxia.
Journal Reference Authors Inoue T
Title Dynamics of calcium and its roles in the dendrite of the cerebellar Purkinje cell.
Journal Reference Authors Adachi N, Kobayashi T, Takahashi H, Kawasaki T, Shirai Y, Ueyama T, Matsuda T, Seki T, Sakai N, Saito N
Title Enzymological analysis of mutant protein kinase Cgamma causing spinocerebellar ataxia type 14 and dysfunction in Ca2+ homeostasis.
Journal Reference Authors Smeets CJ, Jezierska J, Watanabe H, Duarri A, Fokkens MR, Meijer M, Zhou Q, Yakovleva T, Boddeke E, den Dunnen W, van Deursen J, Bakalkin G, Kampinga HH, van de Sluis B, Verbeek DS
Title Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23.
Journal Reference Authors Tulli S, Del Bondio A, Baderna V, Mazza D, Codazzi F, Pierson TM, Ambrosi A, Nolte D, Goizet C, Toro C, Baets J, Deconinck T, DeJonghe P, Mandich P, Casari G, Maltecca F
Title Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.
Journal Reference Authors Mancini C, Hoxha E, Iommarini L, Brussino A, Richter U, Montarolo F, Cagnoli C, Parolisi R, Gondor Morosini DI, Nicolo V, Maltecca F, Muratori L, Ronchi G, Geuna S, Arnaboldi F, Donetti E, Giorgio E, Cavalieri S, Di Gregorio E, Pozzi E, Ferrero M, Riberi E, Casari G, Altruda F, Turco E, Gasparre G, Battersby BJ, Porcelli AM, Ferrero E, Brusco A, Tempia F
Title Mice harbouring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity.
Journal Reference Authors Becker EBE
Title From Mice to Men: TRPC3 in Cerebellar Ataxia.
Journal Reference Authors Hoxha E, Tempia F, Lippiello P, Miniaci MC
Title Modulation, Plasticity and Pathophysiology of the Parallel Fiber-Purkinje Cell Synapse.
Journal Reference Authors Yan H, Pablo JL, Pitt GS
Title FGF14 regulates presynaptic Ca2+ channels and synaptic transmission.
Journal Reference Authors Tada M, Nishizawa M, Onodera O
Title Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias.
Journal Reference Authors Pietrobon D
Title CaV2.1 channelopathies.
Journal Reference Authors Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T
Title Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of SCA6.
Journal Reference Authors Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, Hori S, Kakizuka A, Ichijo H
Title ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats.
Journal Reference Authors Evers MM, Toonen LJ, van Roon-Mom WM
Title Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies.
Journal Reference Authors Ashkenazi A, Bento CF, Ricketts T, Vicinanza M, Siddiqi F, Pavel M, Squitieri F, Hardenberg MC, Imarisio S, Menzies FM, Rubinsztein DC
Title Polyglutamine tracts regulate autophagy.
Journal Reference Authors Chen RH, Chen YH, Huang TY
Title Ubiquitin-mediated regulation of autophagy.
Journal Reference Authors Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT
Title RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.
Journal Reference Authors Rousseaux MWC, Tschumperlin T, Lu HC, Lackey EP, Bondar VV, Wan YW, Tan Q, Adamski CJ, Friedrich J, Twaroski K, Chen W, Tolar J, Henzler C, Sharma A, Bajic A, Lin T, Duvick L, Liu Z, Sillitoe RV, Zoghbi HY, Orr HT
Title ATXN1-CIC Complex Is the Primary Driver of Cerebellar Pathology in Spinocerebellar Ataxia Type 1 through a Gain-of-Function Mechanism.
Journal Reference Authors Jimenez G, Shvartsman SY, Paroush Z
Title The Capicua repressor--a general sensor of RTK signaling in development and disease.
Journal Reference Authors Gennarino VA, Palmer EE, McDonell LM, Wang L, Adamski CJ, Koire A, See L, Chen CA, Schaaf CP, Rosenfeld JA, Panzer JA, Moog U, Hao S, Bye A, Kirk EP, Stankiewicz P, Breman AM, McBride A, Kandula T, Dubbs HA, Macintosh R, Cardamone M, Zhu Y, Ying K, Dias KR, Cho MT, Henderson LB, Baskin B, Morris P, Tao J, Cowley MJ, Dinger ME, Roscioli T, Caluseriu O, Suchowersky O, Sachdev RK, Lichtarge O, Tang J, Boycott KM, Holder JL Jr, Zoghbi HY
Title A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.
Journal Reference Authors Irie T, Matsuzaki Y, Sekino Y, Hirai H
Title Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells.
Journal Reference Authors Bushart DD, Murphy GG, Shakkottai VG
Title Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease.
Journal Reference Authors Hsiao CT, Fu SJ, Liu YT, Lu YH, Zhong CY, Tang CY, Soong BW, Jeng CJ
Title Novel SCA19/22-associated KCND3 mutations disrupt human KV 4.3 protein biosynthesis and channel gating.
Journal Reference Authors Duarri A, Lin MC, Fokkens MR, Meijer M, Smeets CJ, Nibbeling EA, Boddeke E, Sinke RJ, Kampinga HH, Papazian DM, Verbeek DS
Title Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner.
Journal Reference Authors Matilla-Duenas A, Volpini V
Title Spinocerebellar Ataxia Type 37
Journal GeneReviews (1993)
Reference Authors Corral-Juan M, Serrano-Munuera C, Rabano A, Cota-Gonzalez D, Segarra-Roca A, Ispierto L, Cano-Orgaz AT, Adarmes AD, Mendez-Del-Barrio C, Jesus S, Mir P, Volpini V, Alvarez-Ramo R, Sanchez I, Matilla-Duenas A
Title Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37.
Journal Reference Authors Swinnen B, Robberecht W, Van Den Bosch L
Title RNA toxicity in non-coding repeat expansion disorders.
Journal Reference Authors Ishikawa K, Nagai Y
Title Molecular Mechanisms and Future Therapeutics for Spinocerebellar Ataxia Type 31 (SCA31).
Journal Reference Authors Niimi Y, Takahashi M, Sugawara E, Umeda S, Obayashi M, Sato N, Ishiguro T, Higashi M, Eishi Y, Mizusawa H, Ishikawa K
Title Abnormal RNA structures (RNA foci) containing a penta-nucleotide repeat (UGGAA)n in the Purkinje cell nucleus is associated with spinocerebellar ataxia type 31 pathogenesis.
Journal Reference Authors Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A
Title Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement.
Journal Related uah04141 Protein processing in endoplasmic reticulum
KO pathway LinkDB All DBs
