Therapeutic Strategies Targeting Neuronal Metabolic Dysfunction in Neurodegenerative Disorders

Neuronal metabolism is increasingly recognized as a central determinant of vulnerability in neurodegenerative and peripheral nervous system disorders. Mitochondrial failure, impaired substrate utilization, and disrupted metabolic signalling all contribute to synaptic decline, axonal degeneration, and the progressive loss of neural circuit integrity. Advances in multi-omics profiling, live-cell imaging, single-cell energetics, and molecular manipulation techniques have now made it possible to identify disease-specific metabolic signatures with unprecedented resolution. These emerging insights open the door to next-generation therapeutic strategies designed to restore metabolic resilience and prevent disease progression.

This Research Topic aims to highlight recent progress in understanding how metabolic dysfunction drives neuronal pathology and how metabolic pathways can be utilized for neuroprotection across disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and related neurodegenerative conditions. We encourage submissions that integrate molecular mechanisms with translational perspectives, particularly those identifying therapeutic targets, metabolic biomarkers, or circuit-level consequences of metabolic impairment.

Topics of interest include, but are not limited to:

• Molecular mechanisms linking mitochondrial dysfunction, oxidative stress, or impaired energy metabolism to neuronal vulnerability

• Metabolic signatures and pathway dysregulation revealed through transcriptomic, proteomic, metabolomic, or single-cell profiling

• Targeting metabolic pathways (e.g., NAD⁺ biology, lipid metabolism, ketone utilization, mitophagy regulators) to promote neuroprotection

• Interactions between metabolic impairment and synaptic dysfunction, axonal degeneration, or neuroinflammation

• Experimental therapeutics designed to restore metabolic homeostasis in CNS and PNS disorders

• Biomarkers reflecting neuronal metabolic status in preclinical or clinical contexts

• Genetically engineered models or circuit-specific approaches for dissecting energy-related mechanisms

• Innovative tools for manipulating neuronal metabolism, including CRISPR-based screens, biosensors, metabolic reprogramming strategies, small fluorescent dyes and real-time imaging paradigms

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: metabolism, metabolic dysregulation, neuroprotection, neuropathology, neurodegeneration

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.