The Rag GTPases-mTORC1-TFE3 Axis in Kidney Cancer and Neurodevelopment: A Mini Review
Christopher Nardone1,2, Xin Gu3, Stephen J. Elledge1,2*
1Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women’s Hospital, Boston, MA, USA
2Department of Genetics, Harvard Medical School, Boston, MA, USA
3Department of Neurobiology, Harvard Medical School, Boston, MA, USA
The MiT/TFE proteins (MITF, TFE3, TFEB, and TFEC) constitute a family of transcription factors that maintain cellular homeostasis by controlling the transcription of genes involved in lysosomal biogenesis, autophagy, oxidative metabolism, and pigmentation. While significant effort has been placed in understanding the downstream function of this family, the upstream regulation has only recently become clearer. It was appreciated that the nutrient-sensing Rag GTPases-mTORC1 pathway attenuates the activity of this family, but how this occurs mechanistically remained unclear. The physiological role of the MiT/TFE family is underscored by the fact that numerous human diseases are caused by their misregulation. The goal of this minireview is to provide a summary of recent findings that have elucidated how this family is regulated upstream and, hence, the molecular basis of a rare kidney cancer and neurodevelopmental syndrome caused by mutations in TFE3. The information presented here may serve as a framework for future studies.
DOI: 10.29245/2572.942X/2023/1.1287 View / Download PdfExploring the Therapeutic Potential of the Ketogenic Diet on Neurological Disorders: A Comprehensive Review
Sai Krishna Vallamchetla
All India Institute of Medical Sciences, Bhopal, India
The ketogenic diet (KD) has emerged as a promising therapeutic strategy for a variety of neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. The potential benefits of the KD are attributed to its capacity to modulate neurotransmission, reduce inflammation, improve mitochondrial function, and enhance synaptic plasticity. Despite the growing body of evidence supporting the KD's therapeutic potential, there remain challenges in its implementation, such as potential side effects, nutrient deficiencies, and the need for careful monitoring by healthcare professionals. Factors affecting the success of the KD include patient adherence, individual metabolic response, and appropriate diet customization. This review summarizes the current evidence supporting the KD's role in the management of neurological disorders, discusses the underlying mechanisms of action, highlights the challenges and considerations associated with its use, and addresses the factors that can influence treatment success. Further research is needed to optimize the KD for different patient populations, elucidate the specific therapeutic mechanisms, and identify potential biomarkers to predict treatment response, ultimately enhancing the quality of life and overall well-being of individuals affected by neurological disorders.
DOI: 10.29245/2572.942X/2023/1.1286 View / Download Pdf