A new frontier in the fight against Alzheimer’s: the key is in the synapses
A new cellular process could explain the progressive memory loss associated with Alzheimer’s
An Italian team has made a breakthrough discovery that sheds new light on the molecular mechanisms behind Alzheimer’s disease. The study, published in the prestigious journal Embo Reports, identified a new cellular process that could explain the progressive memory loss associated with this neurodegenerative pathology.
Enzyme Dna-Pkcs
At the heart of this discovery is the Dna-Pkcs enzyme, a protein crucial for DNA repair within nerve cells. However, the researchers have shown that DNA-PKCs play a much wider role, extending its influence to synapses, the intricate connections between neurons which enable information transmission.
The key role of synapses
Synapses are, in essence, the contact points between neurons, where chemical and electrical communications take place that underlie all our cognitive functions. Within these highly specialized structures, Dna-Pkcs interact with another fundamental protein, called Psd-95, which is involved in the formation and consolidation of memories.
Through a biochemical process known as phosphorylation, Dna-Pkcs acts as an activator of Psd-95, allowing the latter to effectively perform its role. However, the presence of the amyloid-beta protein, typical of senile plaques characteristic of Alzheimer’s, interferes with this delicate balance.
Beta-amyloid: a molecular saboteur
Beta-amyloid, by accumulating in the brain, inhibits the activity of Dna-Pkcs, preventing it from phosphorylating Psd-95. As a result, Psd-95 becomes less efficient and the synapses progressively weaken. This process, repeated over time, leads to a widespread deterioration of neural connections, with serious repercussions on cognitive abilities.
“It is as if beta-amyloid was a saboteur damaging the cables of an entire power plant,” explains Daniela Merlo, study coordinator. ” When the cables are damaged, the energy cannot flow freely and the whole system goes down”.
New therapeutic perspectives
This discovery opens the way to new and promising therapeutic strategies to combat Alzheimer’s. By intervening in the molecular mechanism identified by the researchers, it may be possible to slow down or even stop the progression of the disease.
“We are talking about an unprecedented opportunity,” says Enrico Garaci. “If we can develop drugs that restore the activity of Dna-Pkcs or protect Psd-95 from the action of beta-amyloid, we could significantly improve patients’ quality of life and lengthen their life expectancy”.
Possible future developments
Based on these results, several research perspectives are opened:
- Identification of new biomarkers: The measurement of Dna-Pkcs and Psd-95 levels could provide a new tool for early diagnosis of Alzheimer’s
- Drug development: The design of molecules capable of modulating the activity of Dna-Pkcs or protecting Psd-95 could lead to the emergence of new therapies
- Studies on other neurodegenerative diseases: This molecular mechanism could be involved in other neurodegenerative pathologies, opening new research perspectives
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