ReviewMolecular neurobiology2026
Focused Ultrasound Modulation of PGC-1α Pathways in Neurological Disease: Mechanistic Rationale and Translational Opportunities.
Review in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
2 authors.
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Abstract
The brain's disproportionate energy demand creates an enduring bioenergetic imperative where mitochondrial performance directly determines synaptic resilience and neuronal survival. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) has emerged as a master transcriptional regulator orchestrating mitochondrial biogenesis, antioxidant defenses, proteostasis, and neuroplasticity, with dysregulation of this axis representing a convergent pathogenic mechanism across Parkinson's disease, Alzheimer's disease, Huntington's disease, stroke, and neuropsychiatric disorders. Despite compelling preclinical evidence, conventional pharmacological PGC-1α activators confront fundamental translational barriers including poor blood-brain barrier penetration, inadequate bioavailability, and off-target metabolic effects. This review synthesizes mechanistic evidence suggesting that focused ultrasound may provide a noninvasive platform for regionally precise modulation of PGC-1α pathways. In this review, focused ultrasound is presented as a proposed upstream modulator of the PGC-1α axis. Existing studies support its ability to induce membrane tension, engage mechanosensitive channels such as Piezo1 and TRAAK, and trigger downstream kinase signaling, but the full ultrasound → PPARGC1A → neuroprotection chain in brain tissue remains a working hypothesis rather than a demonstrated therapeutic mechanism. Indirect priming through reversible blood-brain barrier opening, hemodynamic augmentation, and glial immunomodulation may further facilitate this model. We integrate emerging concepts including the mitochondrial synapse, PGC-1α isoform diversity, and theranostic architectures combining functional ultrasound mapping with targeted sonication. By defining mechanistic opportunities, disease-specific therapeutic strategies, and the sonogenetics frontier, this review proposes a hypothesis-generating roadmap for ultrasonic modulation of PGC-1α-dependent neuroprotection, a drug-free, focal approach that converts acoustic energy into a testable mitonuclear rescue framework requiring direct experimental validation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.