Researchers from King's College London (KCL) claim to have uncovered a link between a molecular scaffold, that allows for interaction between key components of a cell, and the debilitating effects of neurodegenerative diseases. It is possible in the long term that this line of research will yield a new target for tailored treatment in the fight against devastating afflictions such as dementia and motor neuron disease.
The team made the discovery by observing two components of a cell, the mitochondria and the endoplasmic reticulum (ER). The mitochondria is an organelle that produces the majority of the chemical energy used by the cell via the production of adenosine triphosphate. The role of the ER is to make protein and store calcium, which is needed by the cell for signalling processes. It has been discovered that many important functions within a cell are carried out via an interaction between these two cell components.
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Until recently, it was not fully established as to what was responsible for the bond between the mitochondria and the ER. However the team from KCL discovered that the ER created protein VAPB binds with the mitochondrial protein known as PTPIP51 to create a molecular scaffold. This allows for a close association between the two organelles. Furthermore it was found that by increasing the concentration of the two proteins, the researchers could make the bonds grow tighter, thus proving the relationship between the proteins and the molecular scaffold.
"At the molecular level, many processes go wrong in dementia and motor neuron disease, and one of the puzzles we’re faced with is whether there is a common pathway connecting these different processes" states Professor Chris Miller, a member of the Department of Neuroscience at KCL and lead author of the paper on the team's findings. "Our study suggests that the loosening of this ‘scaffold’ between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease."
When an individual is suffering from a neurodegenerative disease, the bonds between the mitochondria and the ER are disrupted, with the result that many of the vital functions carried out via the symbiosis of the mitochondria and the ER are also undermined. With this in mind the researchers observed how the cells of a mouse were affected by the addition of TDP-43, a protein linked to both Amyotrophic Lateral Sclerosis, a form of motor neuron disease, and Fronto-Temporal Dementia, the second most common form of dementia.
It was discovered that the introduction of TDP-43 caused a significant loosening in the molecular scaffolding that binds the mitochondria and the ER, causing the disruption in cell function that comes as the inevitable product of a disease such as dementia. In light of the team's recent findings, future research may attempt to create a targeted drug to combat the breakdown of the scaffold, with the long term aim of creating new, targeted courses of treatment to combat these degenerative diseases.
The research has been published in the journal Nature Communications.
Source: King's College London