Could glial cells be the missing link in treating neurodegeneration?

The mini review brings together emerging evidence showing that glial cells actively influence disease progression and treatment response. Once considered simple support cells, glia are now recognized as dynamic regulators of brain health, playing both protective and harmful roles in neural function.

Over the years, scientists believed that neurons, the cells that send electrical signals, were the main players in brain health and disease. Today, new evidence shows that glial cells are just as important. Olajide’s brief research review shows that glial cells—previously thought to simply “support” neurons—may actually be key to slowing or preventing diseases like Alzheimer’s, Parkinson’s, multiple sclerosis, and others.

The review highlights several promising glia-related therapeutic targets, such as:

Oligodendrocyte dysfunction and myelin breakdown, which contribute directly to the development and progression of Alzheimer’s disease, offering new opportunities for disease-modifying therapies such as remyelination and metabolic support. While recent studies have shown that myelin is more than an axon-insulating structure, it is now recognized as a dynamic contributor to energy metabolism and neuronal survival, with oligodendrocytes being capable of mobilizing fatty acids for ATP production as an alternative to glucose during period of extreme metabolic demand.

Mitochondrial transfer between glial cells and neurons, which may help rescue damaged neurons, opening paths for cell-based intervention. Research has proven that healthy mitochondria can be transferred to dying neurons via the tunnelling nanotubes. This nanotubular system known to be established between cells such as neuron and glia can also facilitate the intercellular transmission of pathological proteins, such alpha-synclein and tau from degenerating neurons to glial cells like astrocytes and microglia.

Extracellular vesicles, tiny structures released by glia, which can transport protective or harmful molecules. In the brain, glial cells use these vesicles to communicate with neurons, especially during stress or injury. Interestingly, scientists are now learning how to “engineer” these vesicles by loading them with protective molecules before they are released to serve as drug delivery.

Senescence of glial cells can contribute to age-related neurodegeneration. Virtually all dividing (mitotic) cells in the body can become senescent with exception is post-mitotic cells, like neurons which do not normally undergo senescence because they no longer divide. However, glial cells, in contrast, can and do become senescent, which is why they are increasingly implicated in age-related neurodegeneration. When they become senescent, they lose these protective functions and even become detrimental. Recent research suggests that this process may not be permanent as class of drugs known as senolytics can selectively remove senescent cells from tissues without harming healthy cells. In experimental models, this approach has been linked to improved brain environment, reduced disease-related pathology, and better neuronal survival. In humans, senolytics have been used as adjunct therapy to slow down neurodegeneration

Glutamate dysregulation is as a driver of neurological diseases through excitotoxicity and neuronal cell death. Astrocytes play a central role in glutamate homeostasis, making them pivotal in therapeutic strategies against excitotoxicity in neurodegenerative disorders. This can be achieved by regulating glutamate transporters, such as excitatory amino acid transporters (EAATs) and their receptors expressed in astrocytes to combat cell death caused by excitotoxicity in glutamate dyshomeostasis.

This review is one of the first in Neuroprotection to bring together a wide range of mechanistic insights on glial cells into a single therapeutic perspective. Rather than focusing only on neurons, as most research in the field does, Olajide’s article highlights the importance of restoring and strengthening glial support systems, marking an important shift toward more comprehensive and holistic approaches to brain repair.

As the global population ages, neurodegenerative diseases are on the rise. Many existing treatments can only manage symptoms temporarily. This review encourages researchers to look more closely at how glial cells behave in different brain diseases and at different stages of life. Glial cells are not passive bystanders in the brain,” Olajide explains. “They actively decide whether neurons survive or die. When their protective roles fail, neurodegeneration accelerates. Therefore, by shifting attention to glial cells, scientists may be able to design therapies that protect the brain at a deeper and more fundamental level.

Olajide recommends that future studies should focus on: understanding why glial cells become harmful in disease, exploring whether boosting glial function can protect neurons, developing therapies using glial mitochondria or extracellular vesicles, and testing drugs that could reverse glial aging.

“This review highlights glial cells as powerful therapeutic drivers rather than passive supporters,” said Olajide. “Targeting glial functions, rather than only neurons, may be an underexplored avenue for combating neurodegenerative disorders.”

About University of Medical Sciences Ondo,

The University of Medical Sciences (UNIMED), Ondo, is Nigeria’s first specialized medical university and the third of its kind in Africa. Founded by the Ondo State Government, UNIMED is dedicated to excellence in teaching, innovative research, and high-quality service delivery. The university offers a comprehensive range of programs across different faculties, including Basic Medical Sciences, Clinical Sciences, Dental Sciences, Nursing Sciences, and Allied Health Sciences. Website: www.unimed.edu.ng

About Tobiloba S. Olajide from University of Medical Sciences

Tobiloba S. Olajide is a young emerging neuroscience researcher at the Laboratory for Experimental and Translational Neurobiology, University of Medical Sciences, Ondo, Nigeria. His work focuses on understanding the molecular basis of neurodegenerative diseases and how new treatment strategies can improve brain health. Olajide is currently investigating on the influence of gut microbiota on co-occurrence of Alzheimer’s risk gene and nickel neurotoxicity using the C. elegans models.

Website: https://letneu.vercel.app/