Using SS-31 (Elamipretide) to Improve Mitochondria Dysfunction and Impairment

Mitochondria are essential components of each cell in the human body. Responsible for generating the energy required for cells to complete their normal and required functions, large scale or systematic mitochondrial dysfunction, when left untreated often results in low energy, cell damage, and eventually cell death. Mitochondrial disease is most often observed in the heart, liver, muscles, kidney, and brain^[1].

Considering the direct role mitochondria have on neuronal function and considering that perioperative neurocognitive disorder (PND) is one of the most commonly experienced and least understood postoperative complications (especially in elderly patients), Zhao et al. examined the specific role of the mitochondria-targeted antioxidant elamipretide (SS-31) has in preventing mitochondrial dysfunction and synaptic and memory impairment caused by oxidative stress and inflammatory responses.

Considering previous research conducted in this specific area, Zhao et al. hypothesized that elamipretide could offer protection against memory impairment experienced during neuroinflammation specifically by offering protection against mitochondrial dysfunction and by reducing oxidative stress and inflammatory response in the hippocampus.

To test this hypothesis, the authors assigned mice to one of four treatment groups: a control plus placebo group, a control plus elamipretide group, a LPS plus placebo group, or a LPS plus elamipretide group before memory performance and hippocampus-related learning were assessed through a series of open field, Morris water maze (MWM), and fear conditioning tests.

Upon completion of all assays, the authors concluded that Elamipretide:

• Protected the hippocampus against LPS-induced mitochondrial dysfunction by maintaining appropriate levels of mitochondrial membrane potential (MMP) and adenosine triphosphate assay (ATP).
• Reduced oxidative stress and the inflammatory response induced by LPS in the hippocampus (of mice).
• Significantly decreased the death of neural cells within the hippocampus of LPS-treated mice.
• Enhanced the hippocampal brain-derived neurotrophic factor (BDNF) pathway and synaptic structural complexity in mice treated with LPS.
• Prevented the reduction of dendritic spines on hippocampus neurons after LPS treatment.

Although mice treated with LPS demonstrated impaired hippocampus-related learning and memory performance, Zhao et al. concluded that memory impairment caused by LPS can be significantly reduced through the introduction of the mitochondria-targeted antioxidant elamipretide. In addition, elamipretide may also have therapeutic potential when it comes to preventing damage resulting from the oxidative stress and neuroinflammation known to contribute to PND. Considering these findings, the authors call for further exploration into the use of mitochondria as a potential treatment strategy for PND.

Source:  (2019, November 20). Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic …. Retrieved from https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1627-9

^[1] “Mitochondrial Disease Clinic – Clinical Genomics – Mayo Clinic.” https://www.mayoclinic.org/departments-centers/clinical-genomics/overview/specialty-groups/mitochondrial-disease-clinic. Accessed 18 Aug. 2021.