DZNE scientists have identified a molecular brake that prevents the regeneration of nerve connections. To this end large sets of genomic data had to be analyzed. This is illustrated in the above figure. Image: DZNE/A. Tedeschi
Releasing molecular brake allowed damaged neurons to regenerate
Injuries to the spinal cord can cause paralysis and other permanent disabilities because severed nerve fibers do not regrow. Now, scientists of the German Center for Neurodegenerative Diseases (DZNE) have succeeded in releasing a molecular brake that prevents the regeneration of nerve connections. Treatment of mice with Pregabalin, a drug that acts upon the growth inhibiting mechanism, caused damaged nerve connections to regenerate.
Researchers led by neurobiologist Frank Bradke report on these findings in the journal Neuron.
Human nerve cells are interconnected in a network that extends to all parts of the body. In this way control signals are transmitted from head to toe, while sensory inputs flow in the opposite direction. For this to happen, impulses are passed from neuron to neuron, not unlike a relay race. Damages to this wiring system can have drastic consequences – particularly if they affect the brain or the spinal cord. This is because the cells of the central nervous system are connected by long projections. When severed, these projections, which are called axons, are unable to regrow.
Reawakening a lost talent
Neural pathways that have been injured can only regenerate if new connections arise between the affected cells. In a sense, the neurons have to stretch out their arms, i.e. the axons have to grow. In fact, this happens in the early stages of embryonic development. However, this ability disappears in the adult. Can it be reactivated? This was the question Professor Bradke and co-workers asked themselves. “We started from the hypothesis that neurons actively down-regulate their growth program once they have reached other cells, so that they don’t overshoot the mark. This means, there should be a braking mechanism that is triggered as soon as a neuron connects to others,” says Dr. Andrea Tedeschi, a member of the Bradke Lab and first author of the current publication.
Searching through the genome
In mice and cell cultures, the scientists started an extensive search for genes that regulate the growth of neurons. “That was like looking for the proverbial needle in the haystack. There are hundreds of active genes in every nerve cell, depending on its stage of development. To analyze the large data set we heavily relied on bioinformatics. To this end, we cooperated closely with colleagues at the University of Bonn,” says Bradke. “Ultimately, we were able to identify a promising candidate. This gene, known as Cacna2d2, plays an important role in synapse formation and function, in other words in bridging the final gap between nerve cells.” During further experiments, the researchers modified the gene’s activity, e.g. by deactivating it. In this way, they were able to prove that Cacna2d2 does actually influence axonal growth and the regeneration of nerve fibers.
Pregabalin triggered neuronal growth
Cacna2d2 encodes the blueprint of a protein that is part of a larger molecular complex. The protein anchors ion channels in the cell membrane that regulate the flow of calcium particles into the cell. Calcium levels affect cellular processes such as the release of neurotransmitters. These ion channels are therefore essential for the communication between neurons.
In further investigations, the researchers used Pregabalin (PGB), a drug that had long been known to bind to the molecular anchors of calcium channels. Over a period of several weeks, they administered PGB to mice with spinal cord injuries. As it turned out, this treatment caused new nerve connections to grow.
“Our study shows that synapse formation acts as a powerful switch that restrains axonal growth. A clinically-relevant drug can manipulate this effect,” says Bradke. In fact, PGB is already being used to treat lesions of the spinal cord, albeit it is applied as a pain killer and relatively late after the injury has occurred. “PGB might have a regenerative effect in patients, if it is given soon enough. In the long term this could lead to a new treatment approach. However, we don’t know yet.”
A new mechanism?
In previous studies, the DZNE researchers showed that certain cancer drugs can also cause damaged nerve connections to regrow. The main protagonists in this process are the “microtubules”, long protein complexes that stabilize the cell body. When the microtubules grow, axons do as well. Is there a connection between the different findings? “We don’t know whether these mechanisms are independent or whether they are somehow related,” says Bradke. “This is something we want to examine more closely in the future.”
The Latest on: Nerve regeneration
[google_news title=”” keyword=”nerve regeneration” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Nerve regeneration
- Glaucoma Awareness Month: Self-care methods to avoid the severity of Glaucomaon January 27, 2023 at 2:32 am
The vision loss in glaucoma is irreversible if left untreated since the optic nerve cannot regenerate once destroyed, unlike other frequent causes of vision loss (like cataracts), where total vision ...
- Propionic acid protects nerve cells and helps them regenerate, shows studyon January 24, 2023 at 8:40 am
Some autoimmune diseases attack the nerves in the arms and legs. Bochum-based researchers are pursuing a new approach to counteracting this damage. Researchers at St. Josef Hospital Bochum have ...
- Nerve Repair and Regeneration Market: Innovations, Opportunities, and Forecaston January 23, 2023 at 9:46 pm
(MENAFN- P&S Intelligence) From $6.2 billion in 2021, the nerve repair and regeneration market size will grow to $17.47 billion by 2030, at a 12.2% CAGR. In recent years, a number of devices and ...
- Therapeutic small molecule can restore visual functions after optic nerve injuryon January 20, 2023 at 10:16 am
Neuroscientists from City University of Hong Kong (CityU) recently identified and demonstrated a small molecule that can effectively stimulate nerve regeneration and restore visual functions after ...
- CityU neuroscientists identify a small molecule that restores visual function after optic nerve injuryon January 20, 2023 at 6:11 am
Traumatic injury to the brain, spinal cord and optic nerve in the central nervous system (CNS) are the leading cause of disability and the second leading cause of death worldwide. CNS injuries often ...
- Molecule Stimulates Regeneration After Optic Nerve Injuryon January 20, 2023 at 2:13 am
Neuroscientists have identified a small molecule that can effectively stimulate nerve regeneration and restore visual functions after optic nerve injury.
- Neuroscientists identify a small molecule that restores visual function after optic nerve injuryon January 19, 2023 at 4:00 pm
Neuroscientists have recently identified and demonstrated a small molecule that can effectively stimulate nerve regeneration and restore visual functions after optic nerve injury, offering great ...
- A Small Molecule That Restores Visual Function After Optic Nerve Injury Identifiedon January 19, 2023 at 10:33 am
Researchers identified a small molecule capable of stimulating nerve regeneration and restoring vision following injury to the optic nerve.
- The Rising Prevalence Of Nerve Repair And Regeneration Expects To Surge The Demand For Biosimilars In The Coming Yearson January 19, 2023 at 8:43 am
From 2022 to 2026, the global nerve repair and regeneration market is expected to grow at an 11% CAGR. The market is currently worth $8 billion and is expected to grow to $12 billion by the end of ...
via Bing News
