In multiple sclerosis
(MS), brain-derived neurotrophic factor (BDNF) provides
neuroprotection, but can also promote disease through the maintenance of
autoreactive T cells. One aspect that has not been explored yet in MS
is related to the opposite functions of BDNF protein isoforms consisting
of the pro-BDNF precursor, which has pro-apoptotic effects, and two
proteolytic isoforms, the mature BDNF with pro-survival effects and
truncated BDNF, with unknown functions. Using ELISA and
semi-quantitative Western-blot we determined the relative serum levels
of BDNF isoforms in 20 relapsing-remitting MS patients without any
disease modifying therapy and 20 age and gender-matched healthy controls
and searched for clinical correlates. Total serum BDNF was lower in MS
than in HC. Using Western-blot analysis, we show that the
percentage of serum mature BDNF and pro-BDNF with respect to total
serum BDNF was significantly decreased, while truncated BDNF was
increased. No correlation between BDNF isoform percentage and clinical
or demographic features was found. Serum Fas (sFas) was increased. These
results support and expand the current hypothesis on the role of BDNF
in multiple sclerosis,
in that low pro-BDNF and high sFas might result in a failure to limit
autoreactive T cells by apoptotic deletion and decreased mature BDNF may
not provide enough neuroprotection, while truncated BDNF percent
increase could be a compensatory mechanism.
Labels: BDNF