Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1

• Published in: Neural regeneration research Vol. 16; no. 3; pp. 448 - 455
• Main Author: Maiese, Kenneth
• Format: Journal Article
• Language: English
• Published: Mumbai Wolters Kluwer India Pvt. Ltd 01.03.2021; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Cellular and Molecular Signaling New York, New York, NY, USA; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: alzheimer’s disease; apoptosis; autophagy; erythropoietin; forkhead; foxo; mechanistic target of rapamycin; silent mating type information regulation 2 homolog 1; Autophagy; Care and treatment; Cellular signal transduction; Development and progression; Genetic aspects; Health aspects; Kinases; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurological research; Review; Transcription factors; United States; FoxO; autophagy; silent mating type information regulation 2 homolog 1; apoptosis; forkhead; mechanistic target of rapamycin; Alzheimer's disease; erythropoietin
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.291382

The global increase in lifespan noted not only in developed nations, but also in large developing countries parallels an observed increase in a significant number of non-communicable diseases, most notable neurodegenerative disorders. Neurodegenerative disorders present a number of challenges for treatment options that do not resolve disease progression. Furthermore, it is believed by the year 2030, the services required to treat cognitive disorders in the United States alone will exceed $2 trillion annually. Mammalian forkhead transcription factors, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), the mechanistic target of rapamycin, and the pathways of autophagy and apoptosis offer exciting avenues to address these challenges by focusing upon core cellular mechanisms that may significantly impact nervous system disease. These pathways are intimately linked such as through cell signaling pathways involving protein kinase B and can foster, sometimes in conjunction with trophic factors, enhanced neuronal survival, reduction in toxic intracellular accumulations, and mitochondrial stability. Feedback mechanisms among these pathways also exist that can oversee reparative processes in the nervous system. However, mammalian forkhead transcription factors, silent mating type information regulation 2 homolog 1, mechanistic target of rapamycin, and autophagy can lead to cellular demise under some scenarios that may be dependent upon the precise cellular environment, warranting future studies to effectively translate these core pathways into successful clinical treatment strategies for neurodegenerative disorders.