Scientists discover a new potential target for the treatment of age-related neurological diseases

Scientists from the Trinity Biomedical Sciences Institute (TBSI) have shed new light on aging processes in the brain. By linking the increased presence of specialized immune cells to conditions such as Alzheimer’s disease and traumatic brain injury for the first time, they have uncovered a possible new target for therapies aimed at treating age-related neurological diseases. .

The research, which benefited from a collaboration with experts from the University of Maryland School of Medicine and focused on microglia in the brain and spinal cord, is published today in an international journal of foreground, Scientific advances.

Microglia are a unique type of immune cell whose job is to support nerve cells, defend against invading microbes, clear debris, and eliminate dying nerve cells by engulfing and eating them. Emerging research indicates that microglia may have different functional responses depending on the molecular and biochemical changes that occur within these specialized cells.

In fact, various subtypes of microglia can be distinguished based on a property called autofluorescence. It is the tendency of cells to emit light of one color after absorbing light of another, and it occurs because specific substances inside cells absorb light. Substances stored in specialized cellular compartments include fat molecules, cholesterol crystals, metals, and other misfolded proteins.

David Loane, assistant professor of neuroscience in the Trinity School of Biochemistry and Immunology at TBSI is the lead author of the research. He said:

“As the brain ages, these materials build up inside the autofluorescent microglia, increasing their autofluorescence. Unfortunately, this buildup of cellular debris also makes it harder for the microglia to perform its tasks. essential for collecting garbage in the brain and preventing neurological disorders, injuries and neurodegenerative diseases.

“In this study, we found – in aged animals – that these microglia adopt a uniquely dysfunctional state, which has a number of problematic impacts. For example, there is increased stress and cell damage, an accumulation of fats and iron, alterations in metabolic processes and an increase in the production of molecules that overload the immune response.”

Additionally, the scientists demonstrated that autofluorescent microglia and associated inflammation were more pronounced in pathological conditions, such as in genetic risk factor models of Alzheimer’s disease, and – promisingly – were reversed by the Drug-assisted microglial replacement in aged animals.

Furthermore, environmental exposure to acute traumatic brain injury in animals accelerated the age of onset and tissue-wide distribution of autofluorescent microglia by increasing oxidative stress damage in the brains of animals. injured animals.

As a result, growing evidence now suggests that the accumulation of autofluorescent microglia contributes to diseases of aging and neurodegeneration. If these microglia subpopulations are highly inflammatory and damage the brain, then targeting them could be a novel strategy for treating age-related diseases. »

David Loane, Assistant Professor of Neuroscience, Trinity School of Biochemistry and Immunology at TBSI