Overview

• The study published in Nature Neuroscience reports that mitoDREADD-Gs, a Gs-coupled designer receptor targeted to mitochondria, increases membrane potential and oxygen consumption in vivo.
• In vivo activation of mitoDREADD-Gs abolished cannabinoid-induced memory alterations and reversed cognitive deficits in two mouse models of Alzheimer’s disease and frontotemporal dementia.
• Researchers present the first direct experimental evidence that impaired mitochondrial activity can causally drive cognitive symptoms in neurodegenerative conditions rather than result from them.
• The mitochondria-targeted tool offers a new platform to probe cellular mechanisms underlying dementia and to guide the development of mitochondrial-focused therapies.
• Authors are planning follow-up experiments to determine whether sustained receptor activation can delay or prevent neuronal loss, while emphasizing that translation to human treatments remains preliminary.