Β‐Lactolin improves mitochondrial function in Aβ‐treated mouse hippocampal neuronal cell line and a human iPSC‐derived neuronal cell model of Alzheimer's disease. Issue 4 (23rd March 2022)

• Record Type: Journal Article
• Authors: Ayabe, Tatsuhiro; Takahashi, Chika; Ohya, Rena; Ano, Yasuhisa
• Is Part Of: FASEB journal. Volume 36:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-23
• Subjects: Alzheimer's disease -- amyloid β -- mitochondria -- neuronal cell; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202101366RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Mitochondrial dysfunctions are a key hallmark of Alzheimer's disease (AD). β‐Lactolin, a whey‐derived glycine–threonine–tryptophan–tyrosine tetrapeptide, has been previously reported to prevent AD‐like pathologies in an AD mouse model via regulation of microglial functions. However, the direct effect of β‐lactolin on neuronal cells and neuronal mitochondrial functions remains unknown. Here, we investigated the effects of β‐lactolin on mitochondrial functions in amyloid β (Aβ)‐treated mouse hippocampal neuronal HT22 cells and human induced‐pluripotent cell (hiPSC)‐derived AD model neurons. Adding β‐lactolin to Aβ‐treated HT22 cells increased both the oxygen consumption rate and cellular ATP concentrations, suggesting that β‐lactolin improves mitochondrial respiration and energy production. Using high content image analysis, we found that β‐lactolin improved mitochondrial fragmentation, membrane potential, and oxidative stress in Aβ‐treated cells, eventually preventing neuronal cell death. From a mechanistic perspective, we found that β‐lactolin increased gene expression of mitofusin‐2, which contributes to mitochondrial fusion events. Finally, we showed that β‐lactolin improves both mitochondrial morphologies and membrane potentials in hiPSC‐derived AD model neurons. Taken together, β‐lactolin improved mitochondrial functions AD‐related neuronal cell models and prevented neuronal cell death. The dual function of β‐lactolin on both neuron and microglia marks an advantage in maintaining neuronal health.