The
presenilin-2 (PS-2) gene was discovered on chromosome 1 and is responsible
for an early onset form of autosomal dominant Alzheimer's disease (AD).
The amino acid sequence is approximately 67% identical with that of the
PS-1 protein. It also is a
membrane protein that has regions where mutations have been identified in
family members with AD. The
gene sequence of PS-2 does not match any known human gene sequences,
except for that of PS-1; but has been found to be a new class of aspartic-proteases.
It has now been identified as one of the (-secretase
proteases.
Alzheimer’s disease (AD) is characterized by the
progressive formation in the brain of insoluble amyloid plaques and
vascular deposits consisting of the 4-kD amyloid $-peptide (A$).
A$
generation is initiated by proteolytic cleavage of the amyloid precursor
protein (APP) at the N-terminal of A$ by $-secretase (BACE).
The A$ peptide is then released by proteolytic cleavage at
its C-terminus by g-secretase (presenilins). Because both these proteases are prime candidates for
therapeutic intervention, an intense search has been underway to identify
these two enzymes.
A
goat antiserum to a synthetic peptide that corresponds to amino acids 31-47
of the N-terminus of human PS-2 protein is currently available. This
antiserum has been shown to be immunoreactive with the unconjugated
immunizing peptide by ELISA, but does not show immunoreactivity with the
immunizing peptide used for the PS-1 antibody. This antibody has
been shown to label neurons in both AD and normal control brains using
paraformaldehyde-fixed, frozen-sections.
This antibody should be a valuable tool for scientists working to
understand the role of PS-2 in AD.
This
antiserum was produced using proprietary methodology whereby the peptide
is attached to a carrier that elicits minimal immunoreactivity so that the
antiserum has a higher degree of specificity for the peptide.
Since there is no overwhelming production of interfering antibodies
to the carrier, this antiserum can routinely be used without further
purification. Pseud-Immune™ control
immune serum (Cat no. GPA018E) from a mock immunized animal is available
to be used in conjunction with this antibody as well as the immunizing
peptide (Cat no. HSP007N), which can be used to neutralize
immunoreactivity.
Manufacturing
Reference:
Southwest Immunology,
Inc., unpublished results.