Shanghai scientists have identified a "brake" gene that could potentially halt the progression of Alzheimer's disease, following the creation of the world's first functional map of regulatory "switches" in astrocytes — cells that protect and support brain neurons — using an innovative technology.

The gene has already been validated in mouse models, where it significantly alleviated cognitive impairments, bringing performance close to that of healthy mice.

The research team said the functional map will be made available to research institutions and pharmaceutical companies worldwide, helping scientists identify similar "brake" genes for other neurological disorders, including Parkinson's disease, amyotrophic lateral sclerosis (ALS) and depression.

The study, a collaboration among researchers from the Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences, Shanghai Sixth People's Hospital and biotechnology firm Genemagic, was published Friday on the website of the journal Science.

Scientists said that in addition to neurons, the brain contains large numbers of astrocytes, which help maintain normal neuronal function. In Alzheimer's disease, however, these cells can become dysfunctional and accelerate neuronal death.

Preventing this harmful transformation depends on identifying the "switches" that control astrocytes — known as transcription factors. With more than 1,000 transcription factors in the human body, pinpointing those critical to astrocyte function has been a major challenge.

In the study, researchers developed an in vivo high-throughput sequencing platform called iGOF-Perturb-seq, enabling large-scale analysis of protein function.

Using adeno-associated viruses engineered to target astrocytes, the team delivered "instruction packages" containing nearly 1,000 transcription factors into astrocytes in the mouse brain. Each package carried a unique barcode.

Scientists then used single-cell sequencing technology to analyze nearly 400,000 astrocytes simultaneously, linking each cell's state to the specific transcription factor it received.

This approach enabled the creation of the first functional map of regulatory "switches" in astrocytes in vivo.

"This map is like a treasure map, helping scientists quickly identify candidate master regulators that can prevent astrocytes from becoming dysfunctional," said Zhou Haibo, the study's lead scientist. "We identified 39 candidate molecules and, after testing, discovered the most potent 'repair master': the transcription factor Ferd3l."

To validate the findings, researchers tested the gene in mice modeling human Alzheimer's disease. Through intravenous injection, they activated the gene in astrocytes. The treated mice showed significant alleviation of cognitive deficits, performing close to healthy mice in object recognition and maze tests.

Further analysis showed that Ferd3l helped astrocytes re-establish healthy interactions with neurons and microglia — the brain's primary immune cells — restoring order and cooperation in the brain's disrupted environment, said Zhang Liansheng, the paper's first author.

Researchers noted that most existing therapies target beta-amyloid plaques, while their study focuses on astrocytes, offering a complementary strategy that could improve treatment outcomes.

An innovative drug targeting beta-amyloid plaques was launched in China in 2025. Clinical evidence supports discontinuing the medication after plaque clearance, while patients continue to benefit. The drug has been included in supplemental public health insurance programs in many cities, including Beijing.

The team said their findings also establish a pool of potential drug targets for neurological diseases, which could be expanded to support the development of precision therapies.

Translating the research into practical applications will be a key focus of future work, Zhou said.