Unwinding the role of senataxin in neurodegeneration.
* At least 115 different mutations in the senataxin (SETX) gene have been identified to cause ataxia.
Mutations in the ALS2, senataxin
, dynactin, angiogenin, optineurin, and spatacsin genes are relatively rare mutations related with FALS (12,13,14).
Other group of genes have been found to be associated with FALS with different mechanism of action such as senataxin
(SETX) and fused in sarcoma (FUS) genes which have roles in RNA processing and alsin gene which is involved in endosomal trafficking and valosin containing protein (VCP) which is involved in protein degradation .
Interestingly, amongst the seven genes that have been identified to cause the disease, most have housekeeping functions, including small heat shock proteins (sHSP) (dHMN-II); glycyl tRNA synthetase (GARS) (dHMN-V); Berardinelli-Seip congenital lipodystrophy (BSCL2) (dHMN-V); immunoglobulin [micro]-binding protein-2 (IGHMBP2) (dHMN-VI); dynactin (DCTN1) (dHMN-VII); and senataxin
(SETX) (dHMN) with pyramidal tract signs.
: Genome Guardian at the Interface of Transcription and Neurodegeneration.
Autosomal dominant inheritance with mutations mapped to chromosome 9p34 in the senataxin
(SETX) gene causes ALS4.
Abbreviations SOD1: Superoxide dismutase 1 ALS2: Alsin SETX: Senataxin
SPG11: Spastic paraplegia 11 FUS: Fused in sarcoma RNA binding protein VAMP: Vesicle-associated membrane protein VAPB: Associated protein B and C ANG: Angiogenin TARDBP: TAR DNA-binding protein FIG4: FIG4 phosphoinositide 5-phosphatase OPTN: Optineurin ATXN2: Ataxin-2 C9ORF72: Chromosome 9 open reading frame 72 VEGF: Vascular endothelial growth factor IFN-[gamma]: Interferon gamma TNF-[alpha]: Tumor necrosis factor ILs: Interleukins IL-1[beta]: Interleukin 1 beta UBC: Ubiquitin C TBK1: TANK-binding kinase 1 SQSTM1: Sequestosome 1 DCTN1: Dynactin subunit 1 IMPAS-1: Histocompatibility minor 13.
21, 35, and 36) presented mutations in SETX (senataxin
), ZFYVE26 (zinc finger, FYVE domain containing 26), and SACS, respectively.