Potential Drug Target for Insomnia and Sleep Apnea: BMAL1 (G406)

Target Name: BMAL1

NCBI ID: G406

BMAL1

Potential Drug Target for Insomnia and Sleep Apnea: BMAL1

BMAL1 (ARNTL) is a protein that is expressed in the brain and is known to play a role in the regulation of sleep-wake cycles. It is a potential drug target for the treatment of sleep disorders, such as insomnia and sleep apnea.

BMAL1 is a member of the BMAL1/NpyR gene family, which encodes a protein that is involved in the regulation of nuclear transport and gene expression. The BMAL1 protein is composed of 215 amino acids and has a calculated molecular mass of 24.1 kDa. It is expressed in the brain and is involved in the regulation of sleep-wake cycles.

BMAL1 is involved in the regulation of the expression of clock genes, which are responsible for controlling the circadian rhythm. It is also involved in the regulation of the expression of genes that are involved in sleep-wake cycle regulation. This makes BMAL1 a potential drug target for the treatment of sleep disorders.

Studies have shown that BMAL1 is involved in the regulation of the length of the sleep-wake cycle. In humans, the sleep-wake cycle is typically between 9 and 12 hours long. However, some people may experience insomnia or sleep apnea, which can disrupt the regulation of the sleep-wake cycle.

Research has shown that BMAL1 is involved in the regulation of the length of the sleep-wake cycle in mammals. For example, studies have shown that BMAL1 is involved in the regulation of the expression of clock genes that encode the period of the sleep-wake cycle. This means that when the length of the sleep-wake cycle is shorter, BMAL1 is involved in the regulation of the expression of clock genes that encode the period of the sleep-wake cycle.

Another study has shown that BMAL1 is involved in the regulation of the expression of genes that are involved in the regulation of sleep-wake cycle. This means that when the length of the sleep-wake cycle is longer, BMAL1 is involved in the regulation of the expression of genes that are involved in the regulation of sleep-wake cycle.

BMAL1 is also involved in the regulation of the release of hormones that are involved in the regulation of the sleep-wake cycle. For example, studies have shown that BMAL1 is involved in the regulation of the release of melatonin, which is a hormone that regulates the sleep-wake cycle. This means that when the length of the sleep-wake cycle is longer, BMAL1 is involved in the regulation of the release of melatonin, which can help to promote sleep.

In addition to its involvement in the regulation of the sleep-wake cycle, BMAL1 is also involved in the regulation of other processes in the brain. For example, studies have shown that BMAL1 is involved in the regulation of the growth and differentiation of neurons, which are responsible for transmitting signals in the brain. This means that when the length of the sleep-wake cycle is shorter, BMAL1 is involved in the regulation of the growth and differentiation of neurons, which can help to improve the functioning of the brain.

Overall, BMAL1 is a protein that is involved in the regulation of the sleep-wake cycle and has the potential to be a drug target for the treatment of sleep disorders. Further research is needed to fully understand the role of BMAL1 in the regulation of the sleep-wake cycle and to develop effective treatments for insomnia and sleep apnea.

Protein Name: Basic Helix-loop-helix ARNT Like 1

Functions: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repressBMAL1 transcription, respectively.BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site

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