Vitamin a modulates neurogenesis-associated pathways and cholinergic signaling in Alzheimer's disease: potential role of reactive astrocytes via NGN2/SOX-11 and SIRT-1.

Authors

Nesrine Saeid El-Mezayen, Yara Alaa Eesa, Wed Alaa Hassan, Dina Ahmed Aly, Yassmen Soliman Saafan, Eman Mahmod Khedr, Aliaa Sherief, Eman Ali Elkordy

Published in

Scientific reports. Volume 16. Issue 1. Jul 25, 2026. Epub Jul 25, 2026.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. A promising regenerative approach involves enhancing endogenous neurogenic capacity within the injured brain. Reactive astrocytes-stellate-like cells in the AD brain-may contribute to a pro-neurogenic environment through transcription factors (TFs) such as neurogenin 2 (NGN2) and SOX-11. This process is tightly regulated by epigenetic mechanisms, particularly SIRT-1, a neuroprotective histone deacetylase that modulates TF activity and neuronal fate. Vitamin A (V_A), a key regulator of differentiation and epigenetic remodeling via its active metabolite retinoic acid, is stored in astrocytes and hepatic stellate cells (HSCs). We hypothesized that AD-related astrocyte activation depletes cerebral V_A, mobilizes hepatic stores, contributes to liver fibrosis, and that V_A supplementation may restore astrocytic function, activate endogenous TFs via SIRT-1, and drive cholinergic neuron regeneration. In a scopolamine (SCO)-induced AD rat model, V_A biodistribution was traced using confocal microscopy. Brain and liver V_A deficiency were confirmed via retinol-binding protein (RBP) and ALDH1A1 expressions. Rats received V_A (1500, 3000, or 4500 IU/kg/day) or donepezil. Outcomes included neurogenesis (DCX), NGN2/SOX-11 expression, SIRT-1 activation, cholinergic regeneration, amyloid-β deposition, and serum tau. Liver fibrosis was assessed via TGF-β, hydroxyproline and histopathologically. AD induced systemic V_A depletion and liver fibrosis. Medium-dose V_A (VAMD) significantly enhanced neurogenesis, TF expression, SIRT-1 activation, cholinergic regeneration, and reversed liver fibrosis. VAMD demonstrated neuroregenerative and antifibrotic effects, indicating a possible therapeutic role in AD.

PMID:
42502106
Bibliographic data and abstract were imported from PubMed on 26 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.