Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives

Abstract

Humanin is a 24-mer peptide first reported in the early 2000s as a new neuroprotective/cytoprotective factor rescuing neuronal cells from death induced by various Alzheimer’s disease-associated insults. Nowadays it is known that humanin belongs to the novel class of the so-called mitochondrial-derived peptides (which are encoded by mitochondrial DNA) and has been shown to exert beneficial cytoprotective effects in a series of in vitro and/or in vivo experimental models of human diseases, including not only neurodegenerative disorders but other human diseases as well (e.g., age-related macular degeneration, cardiovascular diseases, or diabetes mellitus). This review article is focused on the presentation of recent in vitro and in vivo research results associated with the neuroprotective action of humanin as well as of various, mainly synthetic, analogues of the peptide; moreover, the main mode(s)/mechanism(s) through which humanin and humanin analogues may exert in vitro and in vivo regarding neuroprotection have been reported. The prospects of humanin and humanin analogues to be further investigated in the frame of future research endeavors against neurodegenerative/neural diseases have also been briefly discussed.

Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression

“…At Day 6, the top ten overlapping DEGs were upregulated in citalopram-exposed cells. Of these, genes involved in neuroinflammation ( COPS9 ( Tian et al, 2023 )), neuroprotection ( MTRNR2L8 ( Karachaliou and Livaniou, 2023 )) and mitochondrial function ( ATP5MD , NDUFA1 , UQCRQ ) were identified. Interestingly, mitochondrial function is important for neurodevelopment, and dysfunction is known to play a crucial role in the pathogenesis of depression ( Song et al, 2023 ).…”

“…Further, the glutamate transporter SLC7A11 that was also identified in the bulk time-response analysis ( Figure 2C ), was downregulated at Day 10. At Day 13, genes involved in mitochondrial function ( MT-ATP8 ), genes associated with neuroprotection ( MTRNR2L8 , MTRNR2L1 ( Karachaliou and Livaniou, 2023 )), and genes encoding histone variants ( HIST2H2BF , HIST1H4H , HIST1H2BK, HIST1H2AG )) were identified. Of note, HIST1H2AG, has previously been associated with depression ( Tirozzi et al, 2023 ).…”