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Welcome, everyone, to Chapter 13
of this short talk series
on nuclear receptors as
therapeutic targets.
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This chapter deals with
the NR1D receptors
revERB-alpha and revERB-beta,
their biological roles
and their ligands.
The receptor acronym revERBA
originates from the finding
that revERB-alpha is
encoded on the opposite
or reverse strand
of the ERBA gene,
which is an old acronym
for the thyroid hormone
receptor alpha.
There is no similar relation
like this for revERB-beta.
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NR1D receptors play
an important role
in the regulation of
circadian rhythms.
The circadian rhythm is a
cyclic biological process
running approximately 24 hours.
With the circadian rhythm,
for example, alertness and
tiredness, coordination,
body temperature, blood
pressure, hormone levels,
and many other
physiological processes
oscillate over the day.
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Circadian rhythm is
mainly regulated by
the oscillating expression of
transcriptional activators
and repressors,
which form the so-called
circadian clock.
These transcription
factors mutually regulate
their expression levels
and feedback loops.
Additionally, post-translational
modifications,
like phosphorylation,
contribute to their regulation.
The main components
of this system are
the nuclear receptors of
the NR1D family, revERB,
and the NR1F family, ROR,
which we will deal with
in the next chapter.
The transcription
factors are CLOCK,
Circadian Locomotor
Output Cycles Kaput,
and BMAL1,
standing for Basic Helix-Loop-Helix
ARNT-Like protein 1,
which typically also
act as heterodimer,
and the period circadian
protein homologs,
abbreviated as PER,
which are transcriptional
repressors,
as well as the circadian
cryptochromes,
abbreviated as CRY,
which are light-sensitive
flavoproteins
that can also repress
the CLOCK-BMAL1 complex.
