For more than a century, neuroscience told a simple story. Neurons were seen as the main actors behind thought, memory, and emotion, while glial cells were treated as background support. Astrocytes, despite their star-shaped form and wide presence in brain tissue, were described as passive cells that only maintained the environment around neurons.
That story is changing quickly. During the Brain Awareness Week, we explain why astrocytes are moving to the center of neuroscience and becoming a key focus of translational research.
A Different Story of the Brain
New research shows that astrocytes actively regulate synapses, control ion and neurotransmitter balance, and shape how brain networks respond to stress and injury. In other words, astrocytes are not only part of the brain’s structure. They are part of the brain’s decision-making machinery.
This shift is especially visible in recent discoveries often discussed in the field: astrocytes can participate in memory related ensembles, they mediate key neuromodulatory signals such as norepinephrine in functional circuits, and they produce molecules that influence circuit stability in the adult brain. These findings help explain why astrocyte dysfunction is increasingly linked to depression, PTSD, Alzheimer’s disease, and other disorders.
Why P4Health Starts with Astrocytes
The neuroscience pillar of the P4Health Center of Excellence at Łukasiewicz – PORT was built around this exact transition in neuroscience. Within the International Research Agendas (MAB) framework, scientists focus on astrocyte biology as a source of new therapeutic concepts and translational biomarkers.
The main goal is practical, not only descriptive. P4Health is designed to connect molecular findings with objective biological measurements of astrocytes function in preclinical systems, so that promising discoveries can move toward robust validation and future implementation.
How MAB Works
P4Health combines complementary expertise in a unified research program. Dr Agnieszka Krzyżosiak leads work on protein quality control and neurodegeneration mechanisms. Dr Michał Ślęzak develops models allowing real-time monitoring of astrocyte physiology and their impact on neural circuits. Prof. Bastian Hengerer integrates translational neurobiology, biomarker strategy, and preclinical development logic.
The workflow follows two connected phases. First, teams identify mechanisms in astrocyte pathways linked to Alzheimer’s disease, PTSD, and depression. Second, they test interventions and validate effects in cellular and animal systems with objective readouts that can support translational decisions.
Research Tracks in P4Health
Astrocytes in Alzheimer’s Disease
The Alzheimer’s disease track investigates whether failure of astrocytic protein quality control is an early driver of network degeneration. Dr Krzyżosiak’s team tests pathways linked to proteostasis, stress response, and metabolic support, then measures how astrocyte-targeted interventions affect neuronal survival and circuit-level function.
This strategy builds on earlier work in amyotrophic lateral sclerosis (ALS), where pharmacological strengthening of the protein quality control showed clinically relevant potential. As the leader of the Neurodegeneration Mechanisms Research Group explains, “Now we are applying the same logic to Alzheimer’s disease, selectively exploring a new therapeutic space centered on astrocytes. Thanks to a technology that allows us to reprogram cells taken, for example, from a patient’s skin into nerve cells, we can create brain models that preserve the patient’s biological age. We can reproduce the condition of a specific adult individual in the laboratory. Only this level of precision offers hope for therapies that, instead of merely alleviating symptoms, can truly stop degeneration across entire neuronal networks by restoring astrocyte function.”
Astrocytes in Depression
In depression, P4Health focuses on astrocyte metabolism under chronic stress and on mechanisms linked to treatment resistance. This work combines molecular profiling with functional phenotyping to test whether correcting astrocyte metabolism can normalize network function in disease-relevant models.
Dr Michał Ślęzak, the leader of the Biology of Astrocytes Research Group, emphasizes this mechanism directly: “Chronic stress creates chaos in communication between nerve cells and glia, and interrupting this dialogue leads to changes in molecular program of both partners. While most research aims to fix neurons, we came up with several concepts how to do it indirectly, through acting on astrocytes. We will now rigorously test these ideas with our technologies. Restoring balance in the diseased brain would open the way to effective therapies for millions of people for whom currently available medications bring no improvement.”
Cross Disease Biomarkers
The cross-disease biomarker track will be developed by one of the new groups currently being established in P4Health and led by Prof. Bastian Hengerer. It will connect Alzheimer’s disease, PTSD, and depression through shared astrocyte-driven biology. By integrating molecular, electrophysiological, imaging, and biobank-linked data, P4Health aims to build translational biomarker panels that support target prioritization and future patient stratification.
This integrative layer is expected to become a core translational function of Prof. Hengerer’s group, moving from isolated findings to decision-ready evidence in translational neuroscience.
From Molecules to Brain Networks
To bridge mechanism and function, P4Health uses a connected technology pipeline that includes human cell models based on hiPSC platforms, CRISPR perturbation workflows, single cell and single nucleus profiling, MEA electrophysiology, behavioral phenotyping, functional ultrasound (fUS), and linked biobanking workflows.
This integrated design allows teams to move from specific astrocyte pathways to measurable network level effects, instead of treating molecular biology and systems neuroscience as separate worlds.
Why This Matters for Precision Medicine
The ambition of P4Health is to produce assets that can be reused in real translational work: biomarker panels, target prioritization frameworks, standardized protocols, validated datasets, and partnership ready development pathways. The practical objective is to shorten the distance between discovery and high-confidence preclinical decision-making.
