Nat Commun: Increased mitochondrial autophagy protects glucoticoid-induced nerve damage

Increased levels of stress-induced glucoticoids are a major cause of neurodegenerative diseases, such as Alzheimer's disease (AD), which can also cause mitochondrial damage.
In normal neurons, the damaged mitochondrials under asymmetrical fission are removed by autophagy pathways, returned to the cell body to degrade in the lysosome or to be removed at the far end of the axon.
this process is called mitochondrial autophagy, which can help maintain an appropriate number of healthy mitochondrials, especially in synapses.
high concentrations of glucosal hormones can lead to the accumulation of dysfunctional mitochondrials in neurons.
addition, epinephrine, another stress-induced factor, can inhibit autophagy, which may promote mitochondrial dysfunction and neurodegenerative diseases such as AD.
failure to remove damaged mitochondrials can induce synaptic steady-state abnormalities in stress-exposed neurons and eventually lead to neurodegenerative diseases.
recently, researchers at Nature Communications studied the role of glucosal hormones in mitochondrial autophagy suppression and subsequent synaptic defects in hippocellular neurons, SH-SY5Y cells, and ICR mice.
, the researchers observed that glucosal hormones reduce synaptic density and vesicle recovery due to inhibition of mitochondrial autophagy.
screening data showed that glucosin reduced BNIP3 (BNIP3L)/NIX, resulting in reduced mitochondrial respiratory function and synapse density.
noteworthy, the researchers also found that glucosal hormones directly bind glucoticoids to PPC1 alpha initiator, lowering their expression and nuclear transposing.
reduction of PPC1 alpha selectively reduced nix-dependent mitochondrial autophagy.
consistent with these results, mice exposed to corticosteroids pre-treated with NIX enhancer improved mitochondrial autophagy levels and synaptic density in the hippocuple, improving the outcome of spatial memory tasks.
, niX activation may be a potential target for restoring synaptic function by lowering NIX to inhibit mitochondrial autophagy.