The Interplay Between Neuroinflammation and Cellular Stress in Aging and Neurodegeneration: Biomarkers and Therapeutic Strategies

Aging and neurodegeneration research increasingly centers on the intricate interplay between neuroinflammatory responses and cellular stress mechanisms. These processes encompass mitochondrial dysfunction, oxidative damage, proteostasis disruption, and alterations in neuroimmune communication, all of which converge to produce progressive neuronal loss and glial reactivity. While recent studies have illuminated critical roles for microglia, astrocytes, and systemic immune factors, the field still grapples with fundamental questions about how inflammatory and stress-mediated signaling initiate and perpetuate neurodegeneration across diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis. Advancements in imaging, molecular profiling, and neuroimmune modeling have provided a clearer picture of these interactions, yet the translation of this knowledge into clinically relevant biomarkers and therapeutic solutions remains an ongoing challenge. An integrated understanding of these processes is urgently needed to decipher shared molecular pathways that contribute to aging-related brain vulnerability.

This Research Topic aims to elucidate the mechanistic and translational relationships between neuroinflammation, cellular stress, and neurodegenerative progression. It seeks to gather studies that bridge molecular and systemic levels of analysis, exploring how glial activation, mitochondrial impairment, oxidative and endoplasmic reticulum stress, and proteostatic imbalance jointly shape neuronal health and lifespan. By fostering interdisciplinary contributions, from basic mechanistic research to biomarker discovery and therapeutic innovation, this Topic aims to deepen understanding of key cellular drivers of neurodegeneration and identify actionable targets for prevention and intervention strategies. While we encourage breadth across mechanisms, all contributions should center on the interplay between neuroinflammatory and cellular stress responses in the context of brain aging or neurodegeneration. Studies addressing a single pathway in isolation, or conducted in non-neural systems without clear relevance to the aging or degenerating nervous system, are outside the scope of this Topic.

To gather further insights into the dynamic molecular and cellular crosstalk underlying neuroinflammatory and stress-related processes in aging and disease, we welcome articles addressing, but not limited to, the following themes:

- Mechanistic studies of microglia and astrocyte activation in neurodegeneration

- Regulation of mitochondrial function, oxidative stress, and metabolic homeostasis

- Endoplasmic reticulum stress and unfolded protein responses in neuronal survival

- Role of autophagy, proteostasis, and cellular senescence in aging and neurodegeneration

- Identification and validation of biomarkers for disease progression and therapeutic efficacy

- Therapeutic strategies targeting inflammation, oxidative stress, or neuroimmune signaling

- Translational and systems approaches linking mechanistic pathways with clinical outcomes

Accepted article types: Original Research, Reviews, Mini-Reviews, Hypothesis and Theory, Perspectives, and Translational Studies.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Neuroinflammation, Neurodegeneration, Brain aging, Microglia, Astrocytes, Oxidative stress, Mitochondrial dysfunction, Proteostasis, Cellular senescence, Biomarkers, Endoplasmic reticulum stress, Autophagy, Neuroimmune signaling, Glial activation, Therapeutic strategies

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.