S-Nitrosylation of Drp1 Mediates β-Amyloid–Related Mitochondrial Fission and Neuronal Injury Nitric oxide (NO) induces mitochondrial fission and neuronal injury, particularly in the context of Alzheimer's disease (AD). This study shows that β-amyloid (Aβ) triggers mitochondrial fission through S-nitrosylation of dynamin-related protein 1 (Drp1), leading to neuronal damage. S-nitrosylated Drp1 (SNO-Drp1) is increased in AD brains and may contribute to neurodegeneration. The study found that S-nitrosylation of Drp1 occurs in response to Aβ, which is a key mediator of AD. This process is mediated by NO and involves the S-nitrosylation of cysteine residue Cys644 in Drp1. This modification enhances Drp1's GTPase activity, promoting mitochondrial fission and contributing to neuronal injury. The study also identified that SNO-Drp1 formation is associated with increased mitochondrial fragmentation and synaptic damage. The S-nitrosylation of Drp1 at Cys644 is essential for NO-mediated damage and is involved in Aβ-induced synaptic loss. The study further shows that SNO-Drp1 can serve as a biomarker for AD. The study also found that the S-nitrosylation of Drp1 is facilitated by redox-mediated pathways in response to Aβ oligomers, leading to mitochondrial fission and synaptic damage. This process may be exacerbated by increased levels of copper, which is observed in AD brains. The study concludes that S-nitrosylation of Drp1 is a key mechanism in AD pathogenesis, linking oligomeric Aβ, mitochondrial fission, and neuronal damage. Drp1 may represent a potential drug target for the treatment of neurodegenerative disorders involving nitrosative stress and mitochondrial dysfunction.S-Nitrosylation of Drp1 Mediates β-Amyloid–Related Mitochondrial Fission and Neuronal Injury Nitric oxide (NO) induces mitochondrial fission and neuronal injury, particularly in the context of Alzheimer's disease (AD). This study shows that β-amyloid (Aβ) triggers mitochondrial fission through S-nitrosylation of dynamin-related protein 1 (Drp1), leading to neuronal damage. S-nitrosylated Drp1 (SNO-Drp1) is increased in AD brains and may contribute to neurodegeneration. The study found that S-nitrosylation of Drp1 occurs in response to Aβ, which is a key mediator of AD. This process is mediated by NO and involves the S-nitrosylation of cysteine residue Cys644 in Drp1. This modification enhances Drp1's GTPase activity, promoting mitochondrial fission and contributing to neuronal injury. The study also identified that SNO-Drp1 formation is associated with increased mitochondrial fragmentation and synaptic damage. The S-nitrosylation of Drp1 at Cys644 is essential for NO-mediated damage and is involved in Aβ-induced synaptic loss. The study further shows that SNO-Drp1 can serve as a biomarker for AD. The study also found that the S-nitrosylation of Drp1 is facilitated by redox-mediated pathways in response to Aβ oligomers, leading to mitochondrial fission and synaptic damage. This process may be exacerbated by increased levels of copper, which is observed in AD brains. The study concludes that S-nitrosylation of Drp1 is a key mechanism in AD pathogenesis, linking oligomeric Aβ, mitochondrial fission, and neuronal damage. Drp1 may represent a potential drug target for the treatment of neurodegenerative disorders involving nitrosative stress and mitochondrial dysfunction.