Scientists have made a groundbreaking discovery that could potentially reverse memory loss associated with neurodegenerative diseases. Researchers from Inserm and the University of Bordeaux, in collaboration with colleagues from the Université de Moncton in Canada, have successfully established a causal link between mitochondrial dysfunction and cognitive symptoms related to these conditions.

Mitochondria are tiny energy-producing structures within cells that provide the power needed for proper functioning. The brain is one of the most energy-demanding organs, relying on mitochondria to produce energy for neurons to communicate with each other. When mitochondrial activity is impaired, neurons fail to function correctly, leading to progressive neuronal degeneration and eventually, cell death.

In Alzheimer’s disease, for example, it has been observed that impaired mitochondrial activity precedes neuronal degeneration and ultimately, leads to memory loss. However, due to the lack of suitable tools, researchers were unable to determine whether mitochondrial alterations played a causal role in these conditions or were simply a consequence of the pathophysiological process.

In this pioneering study, researchers developed a unique tool that temporarily stimulates mitochondrial activity. By activating G proteins directly in mitochondria using an artificial receptor called mitoDreadd-Gs, they successfully restored both mitochondrial activity and memory performance in dementia mouse models.

“This work is the first to establish a cause-and-effect link between mitochondrial dysfunction and symptoms related to neurodegenerative diseases,” explains Giovanni Marsicano, Inserm research director. “Impaired mitochondrial activity could be at the origin of the onset of neuronal degeneration.”

The tool developed by researchers has opened doors to considering mitochondria as a new therapeutic target for treating memory loss associated with neurodegenerative diseases. Further studies are needed to measure the effects of continuous stimulation of mitochondrial activity and determine its potential impact on symptoms and neuronal loss.

Ultimately, this research holds promise for identifying molecular and cellular mechanisms responsible for dementia, facilitating the development of effective therapeutic targets, and potentially delaying or even preventing memory loss associated with neurodegenerative diseases.

The groundbreaking research conducted at Johns Hopkins University has led to the creation of a novel whole-brain organoid, which is set to revolutionize the field of neuropsychiatric disorders. This miniature human brain, comprising neural tissues and rudimentary blood vessels, is an unprecedented achievement that could lead to a better understanding of conditions such as autism.

Lead author Annie Kathuria, an assistant professor in JHU’s Department of Biomedical Engineering, explained that most previous attempts at growing brain organoids focused on individual regions, such as the cortex or hindbrain. However, their research has succeeded in generating a multi-region brain organoid (MRBO), which represents a significant step forward.

The MRBO retains a broad range of types of neuronal cells, characteristic of a human brain in its early stages of development. This miniature brain weighs around 6 million to 7 million neurons compared to tens of billions found in adult brains. The researchers were able to stick the individual parts together using sticky proteins that act as a biological superglue.

As the tissues began to grow together, they started producing electrical activity and responding as a network. The creation of an early blood-brain barrier formation was also observed, which is essential for controlling molecule passage through the brain.

This breakthrough has far-reaching implications for studying neuropsychiatric disorders such as autism, schizophrenia, and Alzheimer’s disease. Whole-brain organoids will enable researchers to watch disorders develop in real-time, test experimental drugs, and tailor therapies to individual patients. The potential for improved clinical trial success is also substantial, with the current fail rate of 85% to 90% for neuropsychiatric drugs.

Using whole-brain organoids could lead to the discovery of new targets for drug screening and provide a more accurate representation of human brain development. As Kathuria emphasized, “We need to study models with human cells if you want to understand neurodevelopmental disorders or neuropsychiatric disorders.” The creation of this miniature human brain is an exciting step forward in brain research and has the potential to lead to significant advancements in the field.

The scientific community has made significant strides in understanding the complex mechanisms behind Alzheimer’s disease. A recent study by researchers at UC San Francisco has shed light on how microglia, immune cells that play a crucial role in maintaining brain health, can break down and remove toxic proteins associated with the disease. This groundbreaking discovery could pave the way for novel therapeutic approaches to combat Alzheimer’s.

In Alzheimer’s, proteins like amyloid beta clump together, forming plaques that damage the brain. However, in some individuals, microglia effectively engulf and digest these proteins before they can cause harm. The resulting few and smaller clumps are associated with milder symptoms. Researchers at UCSF identified a molecular receptor, ADGRG1, which enables microglia to perform this critical function.

Using a mouse model of Alzheimer’s disease, the researchers observed that the loss of ADGRG1 led to a rapid buildup of amyloid plaques, neurodegeneration, and problems with learning and memory. The study also reanalyzed data from a prior human brain expression study, finding that individuals who died of mild Alzheimer’s had microglia with abundant ADGRG1, whereas those with severe Alzheimer’s had very little ADGRG1.

This discovery has significant implications for the development of new therapies. Since ADGRG1 is one of hundreds of G protein-coupled receptors targeted in drug development, it may be feasible to rapidly translate this finding into new treatments. As Dr. Piao noted, “Some people are lucky to have responsible microglia, but this discovery creates an opportunity to develop drugs to make microglia effective against amyloid-beta in everyone.” The potential for breakthrough therapies is exciting news for those affected by Alzheimer’s and their loved ones.