Rewinding Neurons: A New Way to Protect Motor Neurons in ALS?
- Yiğit Kurtuluş
- Sep 10
- 4 min read
Big idea (in one line): Scientists briefly turned back the molecular “age” of motor neurons and reduced early ALS-like damage in mice.
What They Did?
To tackle the challenge of ALS, the researchers took inspiration from development — specifically, from the genes that originally program motor neurons when we are embryos. Two of the most important “master switches” in this process are called ISL1 and LHX3.
In embryonic life: These transcription factors work together to tell immature stem cells, “You will become a motor neuron.” They shape the neuron’s identity, wiring, and survival skills.
After birth: These genes normally switch off, because the neurons are already formed. But as neurons age, they lose some of their resilience and become more vulnerable to stress and disease.
The research team asked a bold question: what if we turn these embryonic switches back on — not to change the neuron into something else, but just to “remind” it of its younger, tougher state?
How They Did It?
The scientists packaged ISL1 and LHX3 into AAV (adeno-associated virus) vectors, a safe and widely used delivery system in neuroscience.
They designed these vectors with a choline acetyltransferase (ChAT) promoter, so they would specifically target cholinergic motor neurons (the exact cells that ALS attacks).
Newborn mice were injected at postnatal day 1 (P1), ensuring that the genes switched on early in life and before major ALS damage appeared.
They then tested the approach in the SOD1^G93A ALS mouse model, one of the most widely studied genetic models of the disease.
What They Looked At?
The researchers measured:
Gene expression patterns: Did the neurons reactivate developmental programs?
Cell stress markers: Were classic ALS stress aggregates reduced?
Pathology progression: Did the toxic protein SOD1 build up more slowly?
Motor symptoms: Were tremors or weakness delayed?
Neuron survival: Were more motor neurons still alive at later disease stages?
This careful, multi-layered approach showed that “flipping on” developmental switches wasn’t just cosmetic — it had real functional benefits for motor neurons.
What They Found?
Youth-like program reactivated: Motor neurons switched on a more “resilient” genetic program.
Less early stress: Stress aggregates (p62-positive inclusions) dropped dramatically.
Fewer toxic structures: Abnormal ALS-linked SOD1 clumps were much less common.
Delayed symptoms: In some mice, especially females, tremor onset was delayed by about two weeks.
More neurons survived: Higher-dose treatment preserved significantly more motor neurons into disease stages.
Why This Matters?
This is an exciting proof-of-concept: by nudging adult neurons to act a little more like their younger selves, researchers reduced some of the early damage seen in ALS. It’s a targeted, cell-type-specific “partial rejuvenation” strategy — not full reprogramming, but enough to make neurons tougher.
The Road Ahead: What Could This Mean for the Future?
While these results are still in mice, they spark big questions and hopes for the years to come:
Earlier and safer treatments: Could we one day deliver tiny doses of developmental “switches” to strengthen vulnerable neurons before disease takes hold?
Combination therapies: This strategy might be paired with other ALS approaches — like gene silencing or anti-inflammatory drugs — for a more powerful effect.
Beyond ALS: If rejuvenating neurons works here, it could inspire new approaches for other motor neuron diseases, spinal cord injuries, or even age-related decline.
Personalized medicine: One future vision is tailoring these treatments to specific motor neuron subtypes — protecting the ones most vulnerable in ALS.
The ultimate goal? Not just delaying symptoms but truly extending quality of life and independence for patients.
What Really Happens in a Near-Death Experience?
Science is bringing clarity to one of life’s greatest mysteries.
Near-death experiences (NDEs) have fascinated humanity for centuries. People who have survived cardiac arrest, trauma, or other life-threatening crises often describe strikingly similar sensations: moving through a tunnel toward light, floating above their body, or feeling profound peace.
Are these glimpses of the afterlife, or simply the brain under extreme stress? A new neuroscience framework, called NEPTUNE, offers a biological explanation that bridges science with the mystery of consciousness.
The Moment of Crisis
An NDE usually begins when the body faces an extreme threat—such as cardiac arrest, blood loss, or fainting. Oxygen levels plummet, carbon dioxide rises, and the brain’s delicate chemical balance starts to collapse. In these moments, the nervous system enters survival mode, fighting to keep consciousness intact.
A Brain in Overdrive
Paradoxically, instead of shutting down immediately, certain brain regions flare up. Areas linked to memory, self-awareness, and perception can become hyperactive. This abnormal activity may explain why people report vivid imagery, a sense of clarity, or even watching events unfold from outside their own body.
A Chemical Storm
The brain unleashes a cocktail of neurotransmitters during crisis:
Serotonin drives intense visuals and dreamlike states.
Dopamine heightens emotions and feelings of meaning.
Endorphins and GABA induce calm and comfort, reducing fear.
Noradrenaline and acetylcholine make the experience unforgettable, imprinting it in memory as “more real than real life.”
This neurochemical surge closely mirrors what happens during psychedelic trips—suggesting a biological link between altered states of consciousness.
An Evolutionary Defense Mechanism
Some scientists propose that NDEs aren’t random but adaptive. They may be related to thanatosis—a defense mechanism seen in animals that “play dead” under threat. For humans, slipping into a state of calm detachment during trauma may have once helped survival by reducing pain or panic.
Not Only in Death
Interestingly, you don’t need to be at death’s door to experience something similar. Fainting, extreme fear, or the use of psychedelic substances can trigger NDE-like visions. This suggests that it’s not death itself that creates the phenomenon, but rather the brain’s perception of extreme threat.
Memories That Last a Lifetime
Unlike most dreams, NDEs are remembered vividly and often stay with people for decades. This is due to the unusual combination of stress hormones and neurotransmitters that lock these moments into memory, giving them emotional and existential weight.
The NEPTUNE Model
Researchers now group these insights into the NEPTUNE model, which integrates:
Neurobiology (chemical surges, brain activity),
Evolution (ancient defense strategies), and
Psychological factors (personal beliefs and traits).
Together, these mechanisms explain why NDEs feel both universal and deeply personal.
The Mystery Remains
Science shows that NDEs are grounded in biology, not just mysticism. Yet, the fact that our brain can create such profound experiences under stress only deepens the mystery of consciousness. Far from dismissing them, research into NDEs highlights how remarkable—and unexplored—the human mind still is.
Whether you see them as spiritual glimpses or neurobiological events, near-death experiences remind us of the fragile but extraordinary frontier between life and death.
