New Parkinson’s Treatment Target – Drp1 Protein Linked to Sense of Smell – Found in Rat Model, Study Reports

Drp1 Protein Sense of Smell

A new potential target for treating Parkinson’s, a protein named Drp1, has been identified using a rat model of the disease, a study reported.

The target was found to play a central role in the underlying cause of the degeneration and inflammation of nerve cells in the olfactory bulb, the area responsible for the sense of smell. Losing the sense of smell is an early symptom of the progressive neurodegenerative disease. 

The study, “Drp1, a potential therapeutic target for Parkinson’s disease, is involved in olfactory bulb pathological alteration in the Rotenone-induced rat model,” was published in the journal Toxicology Letters.

One early non-motor symptom of Parkinson’s is a loss of the sense of smell. Before it appears in the brain, the toxic buildup of the protein alpha-synuclein — a hallmark of the condition — occurs in the olfactory bulb, which is the the neural structure located above the sinuses that’s responsible for the ability to smell. 

However, the underlying mechanism that leads to early-stage olfactory bulb impairment is unclear.

A common phenomenon in Parkinson’s is the improper functioning of the mitochondria, or the small structures within the cell that produce energy — the cells’ powerhouses. A protein called dynamin-related protein 1 (Drp1) regulates mitochondria dynamics, notably in the cell division process. Chemicals that target this protein have been shown to cause mitochondrial fragmentation leading to the loss of neurons. 

Mitochondrial fragmentation also is known to drive a pro-inflammatory response, a common characteristic of neurodegenerative diseases. 

This prompted researchers to investigate whether Drp1-mediated mitochondrial damage played a role in the impairment of the olfactory bulb. The team used a rat model in which Parkinson-like symptoms were induced by the infusion of rotenone, a mitochondria inhibitor.

To examine the effects of rotenone on the olfactory bulb, a group of rats were treated and compared with a group of untreated rats. In a second experiment, these two groups of animals were compared with a third group treated with a specific Drp1 inhibitor.

Compared with the untreated group, rats treated with rotenone lost more weight and displayed parkinsonian features such as poor motor coordination. The treated rats also had a characteristic depletion of dopamine — the chemical messenger or neurotransmitter produced by dopaminergic neurons that are progressively lost in Parkinson’s disease.

An examination of olfactory tissue under the microscope showed that the density of dopamine-producing neurons was significantly reduced in rotenone-treated rats compared with the untreated group. 

Rotenone triggered the activation of olfactory-specific astrocytes — star-shaped neuroglia or neural support cells — and microglia, a type of brain-specific immune cell. The accumulation of these cells was accompanied by a significant increase in the production of pro-inflammatory markers. 

An examination of the mitochondria in the control animals found typical rod-like shapes characteristic of healthy olfactory cells. In contrast, large numbers of mitochondria in the rotenone-treated group were small and damaged. 

Rotenone injection also caused a dramatic reduction of Drp1 outside of the mitochondria and a significant increase on the inside. 

Finally, the researchers found that adding a Drp1 inhibitor led to a significant reduction in the loss of dopaminergic neurons, increased the presence of healthy mitochondria, and blocked the production of pro-inflammatory markers. 

“In summary, the present findings demonstrate that Drp1-mediated mitochondrial fragmentation induced by rotenone injection participated in neuropathologic changes in the olfactory bulb,” the researchers concluded. 

They said further study needs to be done “to elucidate the network as well as focus on the aberrant mitochondrial dynamics to explore the mechanism.”

The post New Parkinson’s Treatment Target – Drp1 Protein Linked to Sense of Smell – Found in Rat Model, Study Reports appeared first on Parkinson’s News Today.

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