Neurodegeneration Cell by Cell
February 13, 2023
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Neurodegenerative diseases – such as Alzheimer's and Parkinson's – affect more people worldwide than cancer. Yet even though scientists have been studying these diseases for decades, telling the difference between them on a biological level is still a challenge.
Banner image: Blue dopamine neurons and yellow striatal neurons that are part of research into Parkinson's disease. Copyright: Carles Calatayud Aristoy, Patrik Verstreken
.jpg "Common Alzheimer's and Parkinson's Disease Symptoms")
To develop effective therapies for these diseases, scientists need to move away from centuries-old clinical classifications and towards molecular descriptions at a cellular resolution.
The "single-cell revolution" (see box 'Single-Cell Technology') has given scientists incredible insight into how different brain cell types interact with disease. Bart De Strooper, Patrik Verstreken, Roman Praschberger, Sriram Balusu, and Elsa Lauwers at the VIB-KU Leuven Center for Brain & Disease Research wrote the review Neurodegeneration Cell by Cell (published in Neuron) to outline the latest advances in neurodegeneration research at a cellular level.
Brain Cells – More than Just Neurons
When we think about cells in the brain, we tend to think about neurons – but this isn't the only type of cell present in the brain!
.png "There are many different types of neurons in the brain – over 30 in fact! Cartoon created with Biorender.com")
Moving away from a neuro-centric view is essential to moving neurodegeneration research forward. Other types of cells in the brain include microglia, astrocytes, oligodendrocytes, and vascular cells.
Microglia are important in maintaining homeostasis in the Central Nervous System (CNS). Their role in Alzheimer's and Parkinson's has been known for decades, but new studies have brought these brain cells back to center stage. For example, recent work has shown that changes in microglia appear before obvious clinical symptoms of Alzheimer's disease.
.png "Human Stem Cell-Derived Neuronal Progenitors in vitro. Taken by Nóra Baligács from the Bart De Strooper Lab.")
However, studying microglia is no easy task. For instance, it is challenging to culture disease-relevant microglia in vitro (in a test tube or culture dish) that look and behave similarly to those observed in vivo (in living organisms).
Astrocytes are another type of brain cell that play a vital role in disease. Interestingly, astrocytes and microglia have been found to interact with each other in the process of Alzheimer's disease progression, highlighting the importance of studying different kinds of brain cells and how they interact with one another.
A third type of cell that the review mentions are oligodendrocytes. These incredible cells wrap myelin sheaths around axons (a neuron extension) to facilitate electric signal transmission in the brain. When oligodendrocytes don't do their job properly, axons are not optimally maintained, which can cause progressive neurodegeneration. Scientists have observed that neurons in Parkinson's cases are poorly myelinated, linking faulty oligodendrocytes to this disease.
Future Directions
New single-cell technologies such as single nucleus sequencing, soma sequencing, and spatial technologies have helped us to start understanding the complexity of neurodegenerative disease. However, more work is needed to understand exactly how different kinds of brain cells interact with one another in Alzheimer's and Parkinson's.
"Moving forward, concerted efforts across countries and laboratories are required. Initiatives to reduce the administrative burden associated with human data access and sharing, to enable the integration of datasets from different studies, and to facilitate the re-use of code and tools, are critical." - Patrik Verstreken and Bart De Strooper
The single-cell biology revolution will help scientists explore how early a given cell type is involved and whether their reaction contributes to the progression of disease severity. This will provide us insight into which cell types to prioritize for developing targeted therapeutic interventions.
Publication
Neurodegeneration Cell per Cell. Balusu, et al. Neuron, 2023. DOI 10.1016/j.neuron.2023.01.016
