A new research conducted by Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) holds promise for treating and also potentially curing Alzheimer’s disease (AD).
This research involves novel therapeutic target and treatment options based on RNA and small molecules, which could potentially accelerate the drug discovery process.
According to the Department of Science and Technology, AD accounts for 70-80% of dementia cases and is the fifth leading cause of death. The disease is characterised by the accumulation of protein clumps in the brain, memory loss, and cognitive deficits.
Few options now
It added that currently, there are very few therapeutics available in the market, most of which provide only temporary relief. Recently, a few antibody-based drugs were approved, but they offer limited benefits to patients.
“While, the role of various proteins in the development and progression of AD has been well studied, the role of microRNAs (miRNAs) in AD is poorly understood,” it added.
To address this, JNCASR researchers explored altered miRNAs in the AD brain and also probed the potential of miRNAs to be biomarkers for early, specific, and accurate clinical diagnosis of AD.
“Since miRNAs are small non-coding RNA, they are known to target multiple mRNAs to regulate pathways linked to health and diseases as well as multiple disease pathologies linked to AD,” the department said.
Methodology
Madhu Ramesh and Thimmaiah Govindaraju used a double transgenic AD mouse model to discover novel miRNAs involved in AD development and progression and identified various miRNAs that are altered in the AD brain compared to the normal brain, which could potentially trigger the disease.
“The current study offers valuable insight into AD by uncovering the regulatory role of miR-7a in controlling neuroinflammation and ferroptosis via Klf4 targeting,” Prof. Govindaraju said.
The researchers have developed a miRNA-based therapeutic that targets Klf4 to prevent neuroinflammation and ferroptosis.
Natural product
Honokiol is a natural product found in bark and seed cones of the Magnolia tree that targets Klf4 to stall neuroinflammation and ferroptotic cell death involved in AD. The department said that this demonstrates that the miR-7a-Klf4 axis is a novel target for AD and warrants further exploration to develop better therapeutics for the disease.
“The research shows that miR-7a suppresses Klf4, alleviating neuronal damage by modulating inflammation (NF-κB, iNOS, NLRP3), and ferroptosis-related (iron-dependent accumulation of lipid hydroperoxides) pathways. Targeting this axis with a blood–brain barrier-permeable compound like honokiol demonstrates therapeutic potential,” said Gireesh Gangadharan, Departtment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education.
Published – August 06, 2025 10:51 pm IST
