COX5A
Cytochrome c oxidase subunit 5A, mitochondrial precursor (Cytochrome c oxidase polypeptide Va)
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Cytochrome c oxidase subunit Va (COX5A) is involved in maintaining normal mitochondrial function. However, little is known on the role of COX5A in the development and progress of Alzheimer's disease (Martinez-Losa et al., 2018). In this study, we established and characterized the genomic profiles of genes expressed in the hippocampus of Senescence-Accelerated Mouse-prone 8 (SAMP8) mice, and revealed differential expression of COX5A among 12-month-aged SAMP8 mice and 2-month-aged SAMP8 mice. Newly established transgenic mice with systemic COX5A overexpression (51% increase) resulted in the improvement of spatial recognition memory and hippocampal synaptic plasticity, recovery of hippocampal CA1 dendrites, and activation of the BDNF/ERK1/2 signaling pathway [i]in vivo[/i]. Moreover, mice with both COX5A overexpression and BDNF knockdown showed a poor recovery in spatial recognition memory as well as a decrease in spine density and branching of dendrites in CA1, when compared to mice that only overexpressed COX5A. [i]In vitro[/i] studies supported that COX5A affected neuronal growth [i]via[/i] BDNF. In summary, this study was the first to show that COX5A in the hippocampus plays a vital role in aging-related cognitive deterioration [i]via[/i] BDNF/ERK1/2 regulation, and suggested that COX5A may be a potential target for anti-senescence drugs.
Keywords
- BDNF
- COX5A
- ERK1/2
- brain senescence
- memory impairment
- mitochondria