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. 2021 Sep;37(9):1373-1376.
doi: 10.1007/s12264-021-00710-y. Epub 2021 May 27.

Targeting the Transnitrosylation Cascade Provides a Novel Therapeutic Strategy for Alzheimer's Disease

Yi Liu #  1   2 , Gang Wu #  1 , Xiji Shu  3 , Xiaochuan Wang  4   5   6
Affiliations

Targeting the Transnitrosylation Cascade Provides a Novel Therapeutic Strategy for Alzheimer's Disease

Yi Liu et al. Neurosci Bull. 2021 Sep.
No abstract available

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic of Aβ-induced synaptic impairments in AD. Left panel, an increase in NO as a result of toxic Aβ and/or an oxidized milieu leads to SNO-Uch-L1 formation and inhibition of Uch-L1 activity. This altered Uch-L1 activity promotes Aβ production/oligomerization as well as downregulation of the PKA/CREB pathway, resulting in synaptic impairments. Middle panel, Aβ oligomers in turn induce NO generation which then activates the Uch-L1/Cdk5/Drp1 transnitrosylation cascade, leading to mitochondrial dysfunction and synaptic impairments. Right panel, the resulting mitochondrial dysfunction promotes further ROS production and an oxidizing environment, where increased NO generation triggers the transnitrosylation cascade and further disrupts mitochondrial function. Together, this form a vicious cycle where Aβ triggers increased NO production resulting in the Uch-L1/Cdk5/Drp1 transnitrosylation cascade leading to mitochondrial and synaptic impairments, and at the same time increasing Aβ and ROS production, so the cycle continues.
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