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Cytochrome P450-mediated vitamin D and cholesterol metabolism in the pathophysiology of neurodevelopmental disorders

Balachandar Vellingiri1, Masako Kinoshita2, Ajay Elangovan1

  • 1Neurobiology (Ageing and Pediatric) Laboratory, Department of Zoology, Central University of Punjab, India.

The Journal of Steroid Biochemistry and Molecular Biology
|July 17, 2026
PubMed

Insights

Cytochrome P450 (CYP450) enzymes impact neurodevelopmental disorders (NDDs) by regulating brain cholesterol and vitamin D. Targeting these CYP450 pathways offers potential therapeutic strategies for NDDs like autism spectrum disorder (ASD).

Area of Science:

  • Neuroscience
  • Biochemistry
  • Developmental Biology

Background:

  • Cytochrome P450 (CYP450) enzymes are crucial in the central nervous system, not just for liver metabolism.
  • These enzymes regulate vital pathways involving vitamin D and cholesterol, essential for neural development, synaptogenesis, and membrane integrity.
  • Dysregulation in CYP450-mediated pathways is implicated in the pathophysiology of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), Rett syndrome (RTT), and attention-deficit hyperactivity disorder (ADHD).

Purpose of the Study:

  • To review the critical roles of CYP450 enzymes in neurodevelopmental disorders (NDDs).
  • To elucidate the interplay between CYP450 enzymes, vitamin D metabolism, and cholesterol homeostasis in the context of NDDs.
  • To explore the therapeutic potential of targeting CYP450-mediated pathways for NDDs.

Main Methods:

  • Literature review focusing on CYP450 enzymes, vitamin D, cholesterol metabolism, and NDDs.
  • Analysis of the cholesterol-CYP27A1-27-hydroxycholesterol (27-OHC)-liver X receptor (LXR) axis in neurodevelopment.
  • Examination of CYP1A, CYP2B, CYP2C, and CYP3A family contributions to neuroendocrine balance and brain maturation.

Main Results:

  • CYP450 isoforms in the CNS regulate vitamin D and cholesterol, fundamental for neural development.
  • The cholesterol-CYP27A1-27-OHC-LXR axis is a key regulator of neurodevelopment.
  • Aberrant CYP450 activity contributes to synaptic dysfunction, neuronal hyperexcitability, and metabolic imbalance in NDDs.

Conclusions:

  • CYP450 enzymes, vitamin D, and cholesterol homeostasis are mechanistically linked in NDDs like ASD.
  • Targeting CYP450-mediated pathways presents a promising therapeutic avenue for restoring neurodevelopmental and metabolic equilibrium in NDDs.

Keywords:
27-hydroxycholesterolCholesterol homeostasisCytochrome P450Neurodevelopmental disordersOxysterolsVitamin D metabolism

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