Breakthrough RNA therapy offers new hope for Alzheimer’s

New Delhi: Alzheimer’s Disease (AD)—a leading cause of dementia that progressively impairs memory and cognition—may soon have a promising new therapeutic direction. Indian researchers have identified a novel RNA-based pathway that not only holds potential for effective treatment but could also pave the way toward a cure.

The approach involves targeting a key molecular axis using microRNA (miR-7a) and a natural small molecule, Honokiol, to halt neuroinflammation and ferroptosis—two major contributors to AD pathology.

While protein involvement in AD has been extensively studied, the role of microRNAs (miRNAs)—tiny non-coding RNAs that regulate gene expression—is less understood. Researchers from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) explored this gap, identifying altered miRNAs in AD brains and assessing their potential as early diagnostic biomarkers.

Using a double transgenic AD mouse model, Madhu Ramesh and Prof. Thimmaiah Govindaraju found that miR-7awas significantly elevated in AD. This miRNA suppresses Klf4, a master regulator of genes linked to neurodegeneration. The miR-7a–Klf4 axis was shown to influence neuroinflammation and ferroptosis—an iron-dependent form of neuronal cell death—both central to AD progression.

“The study offers valuable insight into Alzheimer’s disease by uncovering the regulatory role of miR-7a in controlling neuroinflammation and ferroptosis via Klf4,” said Prof. Govindaraju.

The team developed a miRNA mimic that effectively reduced Klf4 levels and reversed disease-related changes. In parallel, Honokiol, derived from the Magnolia tree and capable of crossing the blood–brain barrier, was found to pharmacologically target the same pathway, offering a dual approach to AD therapy.

“This research demonstrates that targeting the miR-7a–Klf4 axis can alleviate neuronal damage by modulating inflammatory and ferroptosis pathways,” added Prof. Gireesh Gangadharan of Manipal Academy of Higher Education.

If proven safe and effective in clinical studies, the miRNA mimic and Honokiol could serve as a transformative therapeutic combination—addressing not just symptoms but the underlying causes of Alzheimer’s. The findings also highlight a panel of altered miRNAs that may serve as early diagnostic biomarkers, enabling timely intervention and better patient outcomes.

Beyond AD, this strategy could lead to novel treatments for other neurodegenerative and neuroinflammatory disorders, offering hope to millions worldwide.