Impacting dementia and cognitive loss with innovative strategies: mechanistic target of rapamycin, clock genes, circular non-coding ribonucleic acids, and Rho/Rock

• Published in: Neural regeneration research 2019-05, Vol.14 (5), p.773-774
• Main Author: Maiese, Kenneth
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Cardiovascular disease; Care and treatment; Circadian rhythm; Cognition; Dementia; Diabetes; DNA methylation; Gene expression; Genetic aspects; Kinases; Melatonin; Memory; MicroRNAs; Nervous system; Nucleic acids; Oxidative stress; Protein kinases; Proteins
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.249224

According to the World Health Organization (Dua et al., 2017), the current numbers for the prevalence and treatment costs for dementia worldwide are staggering. Currently, at least five percent of the world’s elderly population, equal to approximately 47 million individuals, have dementia. [...]at least sixty percent reside in low and middle income countries. {Figure 1} The mechanistic target of rapamycin: mTOR, also known as the mammalian target of rapamycin and the FK506-binding protein 12-rapamycin complex-associated protein 1 (FRAP1), oversees the transcription of genes and translation of proteins, proliferation of cells, cellular metabolism, and cellular longevity (Maiese, 2018). mTOR forms part of the complexes mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 has a number components that include Raptor, the proline rich Akt substrate 40 kDa, DEP-domain-containing mTOR-interacting protein, and mammalian lethal with Sec13 protein 8, termed mammalian lethal with SEC13 protein 8 (mLST8). mTORC2 has different components from mTORC1 and includes Rictor, mLST8, DEP-domain-containing mTOR-interacting protein, the mammalian stress-activated protein kinase interacting protein 1, and the protein observed with Rictor-1 (Protor-1) [Figure 1]. mTOR affects neurodegenerative disorders through apoptosis and autophagy (Maiese, 2018). mTOR activation blocks apoptotic cell death in the nervous system and can prevent β-amyloid (Aβ) toxicity that occurs during AD. In regards to the onset of cerebral vascular disease that can lead to cognitive loss, it has been shown that circular antisense non-coding RNA in the INK4 locus in vascular smooth muscle cells and macrophages can block exonuclease-mediated pre-ribosomal RNA processing, ribosome biogenesis, and the proliferation of cells that may lead to atherosclerosis and lead to dementia.