Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.
Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kitakyushu, JP · Author affiliation
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Fukuoka, Japan.Location evidence
Fukuoka, JP · Author affiliation
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Fukuoka, Japan.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
Mitochondrial dysfunction and impairment of high-energy phosphate transfer are increasingly recognised as shared pathogenic features across neurological disorders. Because neurons require large amounts of ATP to sustain synaptic transmission, ion gradients, axonal transport, and intracellular signalling, they are especially vulnerable to disturbances in energy metabolism. Neurological dysfunction, therefore, cannot be explained solely by reduced mitochondrial ATP production. It also involves failure of the creatine kinase/phosphocreatine (CK/PCr) and adenylate kinase/AMP-activated protein kinase (AK-AMPK) systems, which normally support local ATP buffering, high-energy phosphate transfer, and intracellular energy homeostasis. In parallel, extracellular ATP-dependent purinergic dysregulation contributes to glia-mediated inflammation, synaptic dysfunction, and cell death, linking intracellular energy failure to abnormal intercellular signalling. In this review, we integrate these mechanisms into a shared pathological continuum of disrupted energy homeostasis. We then compare Alzheimer's disease, Parkinson's disease, and epilepsy as representative disorders with shared and disease-specific manifestations of this continuum, characterised respectively by chronic cerebral energy crisis, selective metabolic fragility, and acute energy overload with purinergic dysregulation. Finally, we discuss how this comparative perspective may help identify shared therapeutic opportunities while preserving disorder-specific interpretation.