ALS, Prion Disease, and others

ALS, Prion Disease, and Others

Amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig′s disease and motor neuron disease is characterized by progressive degeneration of upper and lower motor neurons. Although the vast majority of ALS cases are sporadic (SALS), almost 10% appear to be familial (FALS).

Studies aiming at finding the genetic origin of ALS have shown that mutations in ALS2/Alsin, senataxin (SETX), and VAMPB (VAPB) genes cause ALS. Additional loci have been identified for ALS (on chromosomes 15, 16, 17, 18, 20 and X) and for ALS with frontotemporal dementia (ALS-FTD). ALS2 is ubiquitously expressed and is abundant in neurons, where it localizes to the cytosolic portion of the endosomal membrane. The function of Alsin is not fully understood, but it is known to act as an exchange factor for Rab5a in vitro, which regulates endosomal trafficking and Rac1 activity. Multiple mutations have been identified in ALS2. Most mutations are predicted to truncate the protein, with the extent of ALS2 truncation reduced in patients with milder phenotype. Loss of ALS2 in mice does not trigger motor neuron degeneration and disease, but predisposes to oxidative stress, and causes age-dependent neurological defects and altered vesicle and endosome trafficking.

ALS2CL (ALS2 C-terminal like) is an ALS2 homologous gene. ALS2CL can interact with ALS2 resulting in a large ALS2-ALS2CL heteromeric complex. It has been suggested that ALS2CL is an important factor modulating the ALS2 and Rab5-mediated endosome dynamics in the cell.

TDP-43 (Tat activating regulatory DNA-binding protein, TARDBP) has been linked to the pathophysiology of ALS and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). The TDP-43 gene encodes a highly conserved DNA/RNA binding protein thought to be involved in RNA transcription and splicing. Abnormal aggregates of TDP-43 and its hyperphosphorylated and N-terminal truncated C-terminal fragments (CTFs) are deposited as major components of ubiquitinated inclusions in most cases of ALS and FTLD-U. The mechanism underlying the contribution of TDP-43 to the pathogenesis of these neurodegenerative diseases remains unknown. Missense mutations in TDP-43 have been found in autosomal dominant ALS families, suggesting that mutant TDP-43 may be a primary cause of motor neuron degeneration. TDP-43 is abnormally phosphorylated in the brain tissue of FTLD-U and ALS patients at TDP-43 [Ser609] and TDP-43 [Ser410]. In addition, TDP-43 undergoes proteolytic cleavage by caspase-3 to generate 25- and 35-kDa fragments when GRN (granulin/PGRN) (a candidate gene for familial FTLD-U) is down-regulated. The 25-kDa C-terminal fragment (CTF) of caspase-cleaved TDP-43 leads to the formation of toxic cytoplasmic inclusions within cells.

It should be noted that mutations in the gene encoding the antioxidant enzyme Cu, Zn superoxide dismutase-1 (SOD-1) have been detected in 20% of FALS patients, however, the association of the cause of SALS and FALS with SOD-1 remains unclear.
Mutations in the ANG (ALS9, Rnase5a), DCTN1 (dynactin 1), NEFH (neurofilament H), or PRPH (peripherin) genes appear to increase the risk of developing ALS. Research findings also suggest that downregluation of SMN1 or SMN2 genes may lead to an increased chance of developing this disorder. It is unclear how variations in these genes lead to increased susceptibility.

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SAB4200136 Anti-ALS2 antibody produced in rabbit polyclonal
affinity isolated antibody
human ... ALS2(57679)
rat ... Als2(363235)
human
WB
SAB4200164 Anti-ALS2CL antibody produced in rabbit polyclonal
affinity isolated antibody
human ... ALS2CL(259173)
mouse ... Als2cl(235633)
rat ... Als2cl(316017)
human
WB
SAB4200165 Anti-ALS2CL (N-terminal) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... ALS2CL(259173)
mouse ... Als2cl(235633)
human
IF, WB
SAB4200166 Anti-ALS2CL (N-terminal region) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... ALS2CL(259173)
human
WB
SAB4200350 Anti-ALS2 (C-terminal) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... ALS2(57679)
mouse ... Als2(74018)
rat ... Als2(363235)
human, rat, mouse
IF, WB
SAB4200137 Anti-ALS2 (N-terminal region) antibody produced in rabbit polyclonal
affinity isolated antibody
mouse ... Als2(74018)
rat ... Als2(363235)
  IF, WB
SAB4200225 Anti-diphospho-TDP-43 [pSer409, pSer410] antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
mouse, human
WB
D0319 Anti-Dorfin (N-terminal) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... RNF19A(25897)
mouse ... Rnf19a(30945)
human, mouse, rat (predicted)
WB
SAB4200310 Anti-Granulin (C-terminal) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... GRN(2896)
human
IF, WB
N2912 Monoclonal Anti-Neurofilament 160/200 antibody produced in mouse RMdO20, monoclonal
purified immunoglobulin
human ... NEFH(4744), NEFM(4741)
mouse ... Nefh(380684), Nefm(18040)
rat ... Nefh(24587), Nefm(24588)
rat, mouse, human
ARR, ICC, IHC, WB
N5389 Monoclonal Anti-Neurofilament 200 antibody produced in mouse NE14, monoclonal
ascites fluid
human ... NEFH(4744)
guinea pig, chicken, mouse, bovine, pig, rat, human, rabbit
ARR, IHC (f), IHC (p), WB
N0142 Monoclonal Anti-Neurofilament 200 (Phos. and Non-Phos.) antibody produced in mouse N52, monoclonal
ascites fluid
human ... NEFH(4744)
mouse ... Nefh(380684)
rat ... Nefh(24587)
wide range
ARR, IHC (f), IHC (p), WB
P5117 Monoclonal Anti-Peripherin antibody produced in mouse 8G2, monoclonal
purified immunoglobulin
human ... PRPH(5630)
mouse ... Prph(19132)
rat ... Prph(24688)
rat, pig, rabbit, feline, bovine, human, mouse
ARR, ELISA (i), IHC, WB
SAB4200223 Anti-phospho-TDP-43 [pSer409] antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
mouse ... Tardbp(230908)
mouse, human
IF, WB
SAB4200224 Anti-phospho-TDP-43 (pSer410) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
mouse ... Tardbp(230908)
human, mouse
WB
S2944 Monoclonal Anti-SMN antibody produced in mouse 2B1, monoclonal
purified immunoglobulin
human ... SMN1(6606), SMN2(6607)
mouse ... Smn1(20595)
Xenopus, mouse, human
ARR, WB
S2147 Monoclonal Anti-Superoxide Dismutase (SOD) antibody produced in mouse SD-G6, monoclonal
ascites fluid
human ... SOD1(6647)
rat ... Sod1(24786)
human, rat, canine
ELISA (i)
SAB2501017 Anti-TARDBP antibody produced in goat polyclonal
affinity isolated antibody
human ... TARDBP(23435)
human
ELISA (i), WB
SAB2102371 Anti-TARDBP (ab1) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
, human, mouse, rat, rabbit, bovine, canine, zebrafish, horse, guinea pig
WB
SAB2102372 Anti-TARDBP (ab2) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
human, rat, guinea pig, mouse, canine, horse
WB
T1705 Anti-TDP-43 antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
mouse, human, rat
IF, IHC, WB
T1580 Anti-TDP-43 (C-terminal) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
rat, human, mouse
IF, IHC, WB
SAB4200006 Anti-TDP-43 (N-terminal region) antibody produced in rabbit polyclonal
affinity isolated antibody
human ... TARDBP(23435)
mouse ... Tardbp(230908)
mouse, human
IF, IHC, WB

Prion Disease

Prion Diseases, or transmissible spongiform encephalopathies (TSEs), are a group of progressive neurodegenerative disorders of the CNS. Rare but fatal, common TSEs in animals are Bovine Spongiform Encephalopathy and Chronic Wasting Disease; examples in humans include Creutzfeldt-Jakob disease and Kuru. The disease is thought to develop when abnormal protein molecules (prions) accumulate in the brain, causing convulsions, ataxia, dementia, and death. TSEs are difficult to diagnose, and lead to dead tissue and sponge-like holes in the brain. Scientists are trying to determine the normal role of prions in the brain, as well as the mechanisms by which they become misshapen and accumulate. TSEs are currently incurable, but the goal is to find ways to block the conversion of normal prion protein to the abnormal form. Sigma-Aldrich offers anti-prion antibodies for prion disease research. Forms include monoclonal purified immunoglobulin and polyclonal affinity isolated antibodies.

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Form

Gene Symbol (ID)

Species Reactivity

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P5999 Monoclonal Anti-Prion Protein antibody produced in mouse IPC1, monoclonal
purified immunoglobulin
mouse ... Prnp(19122)
rat ... Prnp(24686)
mouse, hamster, rat
ARR, WB
P6488 Monoclonal Anti-Prion Protein antibody produced in mouse F89/160.1.5, monoclonal
purified immunoglobulin
bovine ... PRNP(281427)
human ... PRNP(5621)
sheep ... PRNP(493887)
bovine, deer, human, sheep
ELISA (i), IHC, WB
SAB2500823 Anti-PRION Protein (143-153) antibody produced in goat polyclonal
affinity isolated antibody
human ... PRNP(5621)
mouse, canine, rat, human
ELISA (i), WB
P0110 Anti-Prion Protein antibody, Mouse monoclonal 8H4, monoclonal
purified immunoglobulin
bovine ... PRNP(281427)
human ... PRNP(5621)
mouse ... Prnp(19122)
rat ... Prnp(24686)
sheep ... PRNP(493887)
mouse, rat, sheep, human, monkey, bovine
ELISA (i), EM, FACS, ICC, IHC, IP, WB