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Core Circadian Protein BMAL1: Implication for Nervous System Functioning and Its Diseases.

Kristina V Smirnova1, Liudmila P Smirnova1, Tamara G Amstislavskaya2

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The brain and muscle ARNT-like 1 protein (BMAL1) regulates circadian rhythms and impacts nervous system functions. Modulating BMAL1 activity offers a promising therapeutic strategy for various neurological disorders.

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BMAL1circadian rhythmcognitive functionmood disordersneurodegenerationneurodevelopmentneuroinflammation

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Area of Science:

  • Neuroscience
  • Chronobiology
  • Molecular Biology

Background:

  • The brain and muscle ARNT-like 1 protein (BMAL1) is a crucial regulator of circadian rhythms, influencing numerous physiological processes.
  • Disruptions in BMAL1 function are linked to various pathological conditions, including nervous system disorders.
  • BMAL1's evolutionary conservativity enables the use of experimental models to study its role in disease.

Purpose of the Study:

  • To review the multifaceted roles of BMAL1 in the nervous system beyond circadian regulation.
  • To explore BMAL1's involvement in neuroinflammation, neurodegeneration, neurodevelopment, mood disorders, addiction, cognition, and neurosignaling.
  • To summarize BMAL1's biochemical regulation and potential pharmacological interventions.

Main Methods:

  • Comprehensive review of human and animal studies.
  • Analysis of data on BMAL1's function in neurons, glial cells, and microglial cells.
  • Investigation of BMAL1's impact on various neurological processes and disorders.

Main Results:

  • BMAL1 plays significant roles in neuroinflammation, trauma, neurodegeneration, neurodevelopment, myelinization, mood disorders, addiction, cognitive functions, and neurosignaling.
  • BMAL1's functions extend beyond circadian rhythm regulation in diverse neural cell types.
  • Both deficiency and overexpression of BMAL1 can have detrimental or protective effects under pathological conditions.

Conclusions:

  • BMAL1's influence on the nervous system is extensive and complex, extending far beyond its role in circadian rhythms.
  • Therapeutic modulation of BMAL1 activity presents a promising avenue for treating a spectrum of nervous system disorders.
  • Understanding BMAL1's dual protective and destructive roles is key to developing effective neurological treatments.