A significant breakthrough in understanding the mechanisms behind protein accumulation in neurodegenerative diseases such as Alzheimer’s has been achieved by researchers. Through their study on fruit flies, the team discovered that a reduction in mitochondria within neuron axons directly leads to the harmful buildup of proteins.
They identified a crucial factor in this process: an increase in the protein eIF2β. By decreasing its levels, protein recycling was restored, and neuron function improved. This discovery presents a promising new target for therapies aimed at treating conditions like Alzheimer’s and ALS, potentially leading to better outcomes for patients.
Key Points:
1. Depletion of mitochondria in neuron axons results in abnormal protein accumulation, a characteristic feature of diseases like Alzheimer’s.
2. Researchers found that the protein eIF2β plays a significant role in this process, and adjusting its levels could reverse the detrimental effects.
3. Derived from genetic studies in fruit flies, these findings pave the way for developing new treatments that could target mitochondrial health or regulate protein levels to combat neurodegenerative diseases.
Researchers at Tokyo Metropolitan University have unraveled how proteins accumulate abnormally in neurons, a hallmark of neurodegenerative diseases like Alzheimer’s. Their study, conducted using fruit flies, demonstrated that the depletion of mitochondria in axons can directly trigger protein buildup.
Simultaneously, the researchers observed significantly elevated levels of a protein known as eIF2β. Restoring these levels to normal resulted in the restoration of protein recycling. These findings offer promising prospects for new treatments for neurodegenerative diseases.
The team, led by Associate Professor Kanae Ando, sought to uncover the root causes of abnormal protein accumulation by investigating Drosophila fruit flies. These flies serve as a commonly studied model organism due to their physiological similarities to humans.
Their focus was on mitochondria presence in axons, the elongated structures that extend from neurons and facilitate crucial connections for brain signaling. It’s established that mitochondrial levels in axons decrease with age and during the progression of neurodegenerative diseases.
Their research revealed a direct link between axonal mitochondria depletion and protein buildup. Through genetic manipulation to suppress milton production, a protein crucial for mitochondria transport along axons, the team induced abnormal protein levels in fruit fly neurons due to disrupted autophagy, the cellular protein recycling process.
Proteomic analysis identified a substantial increase in eIF2β, a key subunit of the eIF2 protein complex responsible for protein production initiation. Additionally, they observed chemical modifications in the eIF2α subunit, both of which hindered eIF2’s healthy function.
Crucially, by artificially reducing eIF2β levels, the team restored lost autophagy and improved impaired neuron function caused by axonal mitochondria loss. This not only confirms that axonal mitochondria depletion leads to abnormal protein accumulation but also highlights the role of eIF2β upregulation in this process.
Reference:
Original Research:
“Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β” by Kanae Ando et al. eLife