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Drug Development.

Enrico Castroflorio1,2, Joan Cabot1,2, Margalida Suau2

  • 1Laminar Pharmaceuticals S.A., Palma, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Lipid-based compounds, docosahexaenoic acid derivative (DHA-H) and its metabolite (HPA), promote neurogenesis and neuronal maturation. These findings suggest potential lipid-based therapies for neurodegenerative diseases like Alzheimer's disease.

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Area of Science:

  • Neuroscience
  • Lipidomics
  • Neurodegenerative Diseases

Background:

  • Lipids are crucial for neuronal function, and their imbalance contributes to neurodegenerative diseases like Alzheimer's disease.
  • The therapeutic potential of lipid-based interventions for neurological disorders is largely unexplored.

Purpose of the Study:

  • To investigate the effects of a hydroxylated docosahexaenoic acid derivative (DHA-H) and its metabolite (HPA) on neuronal proliferation and differentiation.
  • To explore the underlying mechanisms and potential therapeutic applications in Alzheimer's disease models.

Main Methods:

  • Primary neurosphere culture, immunocytochemistry, immunofluorescence labeling, confocal microscopy, Western blot, and qPCR.
  • In vitro and in vivo studies using 5xFAD mice and wild-type (WT) mice.
  • Analysis of neuronal proliferation and differentiation markers, receptor identification (GPR37), and signaling pathway alterations (MAPK, mTOR).

Main Results:

  • DHA-H and HPA significantly enhance neuronal proliferation (Ki-67, Sox2, Nestin, BrdU incorporation) and differentiation (Doublecortin, NeuroD1, PSA-NCAM) in vitro.
  • In vivo treatment promotes neuronal progenitor cell proliferation in the dentate gyrus of WT and 5xFAD mice.
  • GPR37 receptor upregulation and alterations in MAPK and mTOR signaling pathways were observed, suggesting key mechanisms of action.

Conclusions:

  • Lipid-based compounds DHA-H and HPA demonstrate neurogenic and neuro-maturation effects.
  • These findings support the potential of lipid-based interventions for restoring neurogenesis in neurodegenerative conditions.