Nikhil Prasad Fact checked by:Thailand Medical News Team Jan 20, 2026 1 hour, 45 minutes ago
Medical News: Scientists from Kumamoto University in Kumamoto Japan, including researchers from the Department of Cell Modulation at the Institute of Molecular Embryology and Genetics and the Department of Hematology and Immunology at the Faculty of Life Science, have published an extensive review examining how critical brain signaling systems can both protect and harm nerve cells during aging and disease.
Scientists uncover how restoring balance in brain signaling pathways could slow neurodegenerative diseases
Understanding Brain Survival Signals
The human brain depends on finely balanced chemical messages to keep neurons alive and functioning. One of the most important protective molecules is brain derived neurotrophic factor, commonly known as BDNF. This substance supports neuron survival, learning, memory formation, and the strengthening of connections between brain cells. BDNF works by activating a receptor called TrkB, which then triggers internal signaling routes inside neurons. Among the most important of these routes are the MAPK pathways, especially ERK1 and ERK2, which help decide whether a neuron survives or deteriorates.
When Helpful Signals Become Harmful
The researchers explain that ERK signaling has a dual nature. Brief and well controlled activation helps neurons grow, adapt, and resist daily stress. However, when ERK signaling becomes excessive or remains active for long periods, it can fuel inflammation, synapse loss, and neuronal death. Such prolonged overactivation has been repeatedly observed in neurodegenerative disorders, suggesting that timing and intensity are critical for brain health.
Links to Alzheimer’s Parkinson’s and Huntington’s
In Alzheimer’s disease, falling BDNF levels weaken protective signaling while abnormal ERK activity contributes to memory decline, toxic protein buildup, and loss of brain connections. In Parkinson’s disease, impaired BDNF ERK signaling leaves dopamine producing neurons vulnerable to oxidative damage and protein aggregation. In Huntington’s disease, genetic mutations disrupt both the production and transport of BDNF, starving key brain regions of survival signals and accelerating neuron loss.
Hope from Natural and Drug Based Approaches
This
Medical News report highlights growing evidence that restoring balance to these signaling pathways may slow or even counter disease progression. Several natural compounds have shown promise in experimental studies. Substances such as flavonoids found in fruits and plants have been shown to boost BDNF levels while gently activating ERK signaling in a controlled manner. Compounds like paeoniflorin, cornuside, and extracts from traditional medicinal herbs have demonstrated the ability to reduce inflammation, limit toxic protein accumulation, and improve memory in animal models by normalizing ERK activity. Garlic derived compounds and plant polyphenols such as fisetin have also been shown to enhance neuron survival while reducing harmful stress signaling.
On the drug front, researchers have tested compounds that directly target these pathways. Certain TrkB activating molecules can mimic the effects of BDNF and restore protective ERK signaling. Other drugs aim to suppress excessive activation by blocking upstream enzymes, thereby preventing long lasting ERK overactivity that damages neurons. Experimental inhibitors of p38 and JNK pathways have also shown benefits by reducing inflammation and slowing neuron loss in models of Alzheimer’s and Parkinson’s disease. Importantly, scientists emphasize that effective treatments must carefully fine tune signaling rather than fully switching pathways on or off.
Conclusions
The review strongly suggests that brain health depends on maintaining precise control over BDNF and MAPK signaling. Short bursts of ERK activity are essential for learning and neuron survival, while chronic overstimulation can accelerate neurodegeneration. Future therapies that restore natural signaling balance, whether through diet-based compounds or targeted medications, may offer safer and more effective ways to protect the aging brain and combat neurodegenerative diseases.
The study findings were published in the peer reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/27/2/984
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