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VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin
Humanin (HN) is a 24-residue peptide
displaying a protective activity in vitro against a range of
cytotoxic and neurotoxic insults, as well as mediating in
vivo amelioration of Alzheimer disease (AD)-related
memory impairment in experimental models. Published
evidence suggests that the mechanisms through
which HN exerts its cyto- and neuroprotective activity
may include its secretion and binding to membraneassociated
receptors. Here, we describe the identification
of a new modulator of HN neuroprotective activity,
V-set and transmembrane domain containing 2 like
(VSTM2L), previously known as C20orf102. VSTM2L
interacts with HN in both yeast and mammalian cells, is
secreted in cultured cells, is present in serum, and is
selectively expressed in the central nervous system.
VSTM2L colocalizes with HN in distinct brain areas as
well as in primary cultured neurons, where it plays a
role in the modulation of neuronal viability. When
tested in HN neuroprotection bioassays, VSTM2L acts
as a strong antagonist of HN neuroprotective activity.
In summary, VSTM2L is the first example of a secreted
antagonist of HN and may play a role in the modulation
of HN biological function