SIK3-HDAC4 signaling pathway: the switch for transition between sleep and wakefulness

Sleep is an essential physiological process vital to maintaining overall well-being. The reticular activating system (RAS), a network of neurons in the brainstem, regulates wakefulness and sleep. While it may seem passive, sleep consists of distinct cycles, each with its unique characteristics and functions. Two key sleep phases are non-rapid eye movement (NREM) and  rapid eye movement (REM).
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

Sleep, an essential biological state, involves significant reductions in physical activity, sensory awareness, and interaction with the environment. This complex physiological process is primarily regulated by specific brain regions, notably the hypothalamus and pons, which govern the sleep-wake cycle or circadian rhythm.
The circadian rhythm, a nearly 24-hour cycle, is deeply influenced by environmental light cues. Light exposure directly affects the hypothalamus, which in turn regulates...

Sleep progresses through distinct stages, each characterized by specific brain wave patterns and physiological responses ranging from wakefulness to stages of non-rapid eye movement, known as non-REM, to rapid eye movement, referred to as REM. Understanding these stages helps in recognizing how sleep supports various bodily and cognitive functions.
Before sleep begins, in wakefulness, the brain exhibits primarily beta waves, which are high in frequency and low in amplitude, indicating alertness...

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...

REM Sleep Behavior Disorder (RBD) is a sleep disorder characterized by the absence of muscle paralysis that normally occurs during the REM phase of sleep. This absence allows individuals to physically act out their dreams, which are often vivid and disturbing. Common behaviors exhibited during episodes include kicking, punching, and yelling. These actions can be dangerous, potentially leading to injuries for the person with RBD or their bed partner.
RBD is significantly associated with...