Potential Therapy for Alzheimer's Disease: Modulating Tunneling Nanotube Dynamics Restores Mitochondrial Transport and Ameliorates Aβ-induced Toxicity.

The development of therapies for Alzheimer's disease (AD) has long been constrained by the limitations of single-target strategies. Based on the core pathological features of AD-the cascade amplification effects of β-amyloid (Aβ) transcellular transport and mitochondrial dysfunction-combined with recent breakthrough discoveries: ① In vivo observation of tunneling nanotubes (TNTs) formation in the cerebral cortex of mouse models, ② Aβ-induced TNTs formation, ③ TNTs-mediated intercellular propagation of Aβ pathology, ④ TNTs-driven compensatory transfer of functional mitochondria between cells, this review proposes an innovative dual-directional regulatory strategy that precisely targets the molecular mechanisms of TNTs to simultaneously suppress Aβ pathological propagation and enhance mitochondrial rescue in diseased cells. By systematically elucidating: ① The molecular mechanisms underlying TNTs-mediated specific transport of Aβ and functional mitochondria, ② The molecular basis for directional regulation of TNTs transport, this strategy aims to develop potential therapeutic agents for AD, offering a novel intervention paradigm to overcome the current therapeutic impasse in AD treatment.