Nano-Brake Halts Mitochondrial Dysfunction Cascade to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits.

ABSTRACT: Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation of mitochondrial calcium ion (Ca²⁺ ) homeostasis and the mitochondrial permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to the mitochondrial dysfunction cascade in AD pathogenesis. Herein, a "two-hit braking" therapeutic strategy to synergistically halt mitochondrial Ca²⁺ overload and mPTP opening to put the mitochondrial dysfunction cascade on a brake is proposed. To achieve this goal, magnesium ion (Mg²⁺ ), a natural Ca²⁺ antagonist, and siRNA to the central mPTP regulator cyclophilin D (CypD), are co-encapsulated into the designed nano-brake;

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC9982524 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature