Mitochondria keep your brain cells alive – helping them function easily can protect against Parkinson’s disease

In 1817, a British physician named James Parkinson published An essay on shaking palsyduring which cases of a neurodegenerative disease were first described, which is now generally known as Parkinson's disease. Today, Parkinson's disease is the second commonest neurodegenerative disease About 1 million Americans are affected within the United States and greater than 10 million people worldwide.

The typical tremor in patients with this disease is the results of dying brain cells that control movementTo date, there aren’t any treatments that may stop or decelerate the death of those cells.

We are Researchers who study Parkinson's diseaseFor over a decade Our laboratory has investigated the role that mitochondria – the facility plants that offer cells with energy – play in Parkinson’s disease.

Our research has identified a key protein which may lead to recent treatments for Parkinson's disease and other brain diseases.

Mitochondrial dynamics and neurodegeneration

Unlike real power plants, whose size and site are fixed, mitochondria are more dynamic. Their size, number and site are always changing they usually migrate between many alternative parts of the cell to satisfy different demands. These Mitochondrial dynamics are crucial not just for mitochondrial function but additionally for overall cell health.

A cell is sort of a factory. For smooth operation, multiple departments must work together seamlessly. Since many vital processes are interconnected, impaired mitochondrial dynamics can trigger a domino effect between departments and vice versa. Collective dysfunction in numerous parts of the cell ultimately results in cell death.

Recent studies have linked imbalances in mitochondrial processes to varied neurodegenerative diseasesincluding Parkinson's diseaseIn many neurodegenerative diseases, certain disease-related aspects corresponding to toxic proteins and environmental neurotoxins disrupt the harmony of mitochondrial fusion and fission.

Disturbed mitochondrial dynamics also affects the Cleaning and waste recycling processeswhich results in an accumulation of toxic proteins that form harmful aggregates inside the cell. In Parkinson’s, the presence of those toxic protein aggregates is a Characteristics of the disease.

Parkinson's disease through targeted treatment of mitochondria

Our team hypothesized that restoring mitochondrial function by manipulating their very own dynamics could protect against neuronal dysfunction and cell death.

To restore mitochondrial function in Parkinson’s, we focused on a key protein that controls mitochondrial dynamics: Dynamin-related protein 1 or Drp1. This protein is of course abundant in cells and travels to mitochondria as they divide into smaller sizes for greater mobility and quality control. However, an excessive amount of Drp1 activity results in excessive division, leading to fragmented mitochondria with impaired function.

Using various laboratory models of Parkinson’s disease, including neuronal Cell cultures and rat and mice Models we found that the presence of environmental toxins and toxic proteins linked to Parkinson's caused mitochondria to change into fragmented and dysfunctional. Their presence was also related to the buildup of those same toxic proteins, which worsened the health of neuronal cells until they eventually began to die.

We also observed behavioral changes in rats that affected their movements. However, by reducing the activity of Drp1, we were in a position to Restore mitochondria to their normal activity and performance. Their neurons were protected against disease and will proceed to operate.

In our study for 2024, we found a Additional advantages the targeted targeting of Drp1.

We used neuronal cells Manganese, a heavy metal related to neurodegeneration and an increased risk of Parkinsonism. Surprisingly, we found that manganese harmful to the cell's waste recycling system than to its mitochondria, resulting in the buildup of toxic proteins before the mitochondria lost their functionality. However, by inhibiting Drp1, the waste recycling system was restarted and toxic proteins were eliminated despite the presence of manganese.

Our results show that inhibiting Drp1 in a couple of pathway could protect cells from degeneration. Now now we have identified several FDA-approved compounds that focus on Drp1 and are testing them as potential treatments for Parkinson's.