Neurodegenerative Disease: New Treatment Target Found
- A protein identified by UT Southwestern Medical Center researchers appears to control reactive gliosis,a condition linked to several neurodegenerative diseases.The findings, published in neuron, could pave the way...
- Chun-Li Zhang, professor of molecular biology, who co-led the study with Tianjin Shen, research scientist, said reactive gliosis can either help the nervous system adapt to stress or...
- Glia, non-neuronal cells, make up over half the central nervous system's volume, supporting neurons by providing nutrients, insulation, and removing pathogens.
UT Southwestern scientists have pinpointed GADD45G as a “master regulator” of reactive gliosis, a critical finding with profound implications for treating neurodegenerative diseases. This groundbreaking research reveals that controlling GADD45G activity could hold the key to mitigating the damaging effects of reactive gliosis, a condition implicated in Alzheimer’s, Parkinson’s, and Huntington’s. The study, published in Neuron, shows that manipulating this protein can either exacerbate or alleviate symptoms in mouse models. The implications are significant, as researchers observed that in Alzheimer’s models, deleting GADD45G improved cognition.News Directory 3 is following this story closely. Could targeted therapies modulating GADD45G activity revolutionize neurodegenerative disease treatment? Discover what’s next.
‘Master Control Switch’ Protein Offers New Neurodegenerative Disease Treatment Target
Updated May 29, 2025
A protein identified by UT Southwestern Medical Center researchers appears to control reactive gliosis,a condition linked to several neurodegenerative diseases.The findings, published in neuron, could pave the way for new treatments for Alzheimer’s, parkinson’s, Huntington’s, and other related conditions.
Chun-Li Zhang, professor of molecular biology, who co-led the study with Tianjin Shen, research scientist, said reactive gliosis can either help the nervous system adapt to stress or become harmful, even causing neuronal death. Learning to control this condition could protect cells and alter the course of neurodegenerative disease, Zhang said.
Glia, non-neuronal cells, make up over half the central nervous system’s volume, supporting neurons by providing nutrients, insulation, and removing pathogens. Astrocytes and microglia are common types of glial cells. When the central nervous system experiences stress from trauma or disease, these cells proliferate, grow larger, secrete protective proteins, absorb harmful factors, and reinforce the blood-brain barrier, all signs of reactive gliosis.
Though, Zhang explained that reactive gliosis can also damage connections between neurons, restrict axon regeneration, increase neuroinflammation, and trigger cell death. These negative effects are believed to contribute significantly to neurodegenerative disease pathology.
Researchers focused on Gadd45g,a gene whose activity increased significantly in astrocytes exposed to a bacterial toxin. Gadd45g is part of a family of genes known as stress sensors in cancer research,but its role in healthy astrocytes was previously unclear.
Experiments with mice showed that overproducing GADD45G, the protein product of the Gadd45g gene, spurred reactive gliosis not only in modified astrocytes but also in nearby unmodified cells. This suggested that astrocytes secreted chemical signals to induce reactive gliosis in other cell types, a theory confirmed in lab experiments.
The researchers also found increased Gadd45g activity in the brains of mice with severe Alzheimer’s disease, supporting the idea that the gene triggers reactive gliosis in the disease. Analysis of gene activity in people with Alzheimer’s confirmed that this gene is upregulated in human patients as well.
When the researchers genetically modified the mouse model to produce more GADD45G,symptoms of Alzheimer’s worsened,with increased amyloid-beta protein and inflammation. Conversely, deleting Gadd45g in astrocytes reduced amyloid-beta protein and enhanced cognition in the Alzheimer’s model, improving learning and memory.
Zhang said these results suggest GADD45g acts as a master regulator of reactive gliosis. Controlling its activity could possibly improve outcomes for Alzheimer’s and other neurodegenerative diseases.
Other UT Southwestern researchers who contributed to this study are Wenjiao Tai, Shuaipeng Ma, Xiaoling Zhong, Yuhua Zou, and Dongfang Jiang.
What’s next
Future research will focus on developing targeted therapies to modulate GADD45G activity, potentially leading to new treatments for neurodegenerative diseases by controlling reactive gliosis and its detrimental effects on brain function.