Antibodies for Amyotrophic Lateral Sclerosis - FocusOn 133

Amyotrophic Lateral Sclerosis (ALS) is described as a neurodegenerative disease and characterized by degeneration of upper and lower motor neurons. ALS is specified by mid-to-late-life onset, selective neuronal death and the formation of protein deposits in affected neuronal tissues similar to other neurodegenerative diseases (Alzheimer's disease: FocusOn 130, Parkinson's disease: FocusOn 131, Huntington's disease: FocusOn 132). Sporadic cases of ALS occur with no family history of ALS. Familial ALS is due to inherited mutations spread throughout the SOD1 polypeptide.

Superoxide Dismutase (SOD)

SOD is an antioxidant enzyme and as such part of the defense system against reactive oxygen species. SOD catalyses the dismutation reaction of the superoxide radical anion (O2-) to hydrogen peroxide (H2O2) through glutathione reductase and catalase. Several classes of SODs have been identified, which include the intracellular copper/zinc SOD (Cu/Zn-SOD, SOD1), the mitochondrial manganese SOD (Mn-SOD, SOD2) and the extracellular copper/zinc SOD (ECSOD, SOD3).

SOD1 is found in all eukaryotic species as a homodimeric 32 kDa enzyme, which contains one Cu- and one Zn-ion each. SOD1 neutralizes supercharged oxygen molecules (superoxide radicals), which can damage cells if their levels are not controlled. The mechanism through which mutant SOD1 causes ALS is not known, but instability, misfolding and aggregation of mutant SOD1 is hypothesized. Biochemical markers of SOD1 misfolding have been noticed as early indicators of ALS. One such marker is the appearance of detergent insoluble precipitates of SOD1 which correlate well with disease onset and progression.

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Fig. 1: Staining of mouse brain lysate with SOD1 antibody Cat.-No. AP16583PU-N

Fig. 2: Western blot analysis of SOD1 antibody (center) in Jurkat cell line lysates (35 µg/lane). SOD1 (arrow) was detected using the purified antibody Cat.-No. AP18205PU-N

TAR DNA-binding Protein 43 (TARDBP, TDP-43)

The cellular protein TARDBP functions as a DNA-binding protein and specifically binds to the TAR DNA sequence motifs of HIV. TARDBP protein has been identified as a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions with or without motor neuron disease. Therefore, TARDBP defines a novel class of neurodegenerative diseases called TARDBP proteinopathies.

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Fig. 3: Paraffin embedded sections of human prostate cancer were incubated with human TARDBP antibody Cat.-No. AM09038PU-N

Fig. 4: Formalin-fixed, paraffin-embedded (FFPE) breast tissue stained with TARDBP antibody Cat.-No. AP08534PU-N

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Fig. 5: Cell lysates of HeLa were resolved by SDS-PAGE, transferred to NC membrane and probed with anti-human TARDBP antibody Cat.-No. AM09038PU-N

Fig. 6: Staining of Jurkat lysate with TARDBP antibody Cat.-No. AP16884PU-N

Key References

 

Cairns NJ et al, Jul 2007, Am J Pathol 171(1): 227-240

 

Eisen A et al, Apr 2008, Amyotroph Lateral Scler 9(2): 108-119

 

Geser F et al, Feb 2009, Arch Neurol 66(2): 180-189

 

Jonsson PA et al, Jan 2004, Brain 127(Pt 1): 73-88

 

Koyama S, 2006, Biochem Biophys Res Commun 343(3): 719-30

 

Pesirids, GS et al, Oct 2009, Hum Mol Genet 18(R2): R156-162

 

Proescher, JB et al, Jun 2008, Hum Mol Genet 17(12): 1728-1737

 

Valentine, JS et al, Apr 2003, Proc Natl Acad Sci USA100(7): 3617-3622

Further readings

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