Cognitive impairment with diabetes mellitus and metabolic disease: innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways

Abstract

Introduction: Dementia is the 7 th leading cause of death that imposes a significant financial and service burden on the global population. Presently, only symptomatic care exists for cognitive loss, such as Alzheimer's disease.Areas Covered: Given the advancing age of the global population, it becomes imperative to develop innovative therapeutic strategies for cognitive loss. New studies provide insight to the association of cognitive loss with metabolic disorders, such as diabetes mellitus.Expert Opinion: Diabetes mellitus is increasing in incidence throughout the world and affects 350 million individuals. Treatment strategies identifying novel pathways that oversee metabolic and neurodegenerative disorders offer exciting prospects to treat dementia. The mechanistic target of rapamycin (mTOR) and circadian clock gene pathways that include AMP activated protein kinase (AMPK), Wnt1 inducible signaling pathway protein 1 (WISP1), erythropoietin (EPO), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) provide novel strategies to treat cognitive loss that has its basis in metabolic cellular dysfunction. However, these pathways are complex and require precise regulation to maximize treatment efficacy and minimize any potential clinical disability. Further investigations hold great promise to treat both the onset and progression of cognitive loss that is associated with metabolic disease.

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

“…Dementia in the United States affects greater than 5 million people [4]. Many of these cases, 60 percent, are diagnosed as AD [4,6,17,[40][41][42][43]. Case of AD that are familial in origin comprise under 2% of all cases [4].…”

“…Yet, there exist other risks for developing vascular cognitive loss that can affect the efficacy of treatments such as tobacco use, alcohol consumption, hypertension, and a low level of education [20,39,[54][55][56][57]. With reference to metabolic disease, tight glucose control in the serum in combination with early diagnosis of DM may assist to limit the progression of the disease, but complications from DM can still ensue [6,[58][59][60][61][62][63][64][65][66][67][68][69]. Given the need for novel strategies directed against memory loss and dementia, exciting new avenues of development are now focusing upon biological clock mechanisms and include the pathways of the mechanistic target of rapamycin (mTOR), its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), the growth factor erythropoietin (EPO), and the wingless pathway of Wnt pathway (Fig.…”

“…Biological clocks and circadian rhythm pathways are vital components in the onset of nervous system disorders, memory loss, and dementia [6,34,39,[70][71][72][73][74][75][76] (Table 1). Changes in the function of biological clock pathways can impact cellular metabolic homeostasis [6,[76][77][78][79][80][81][82][83][84][85], cancer [6,80,81,84,[86][87][88][89], energy metabolism and aging [70,74,77,84,90], mitochondrial energy maintenance [76,81,91,92], renal disease [78,86], and viral diseases [72,[93][94][95][96][97][98][99][100]…”

“…Changes in the function of biological clock pathways can impact cellular metabolic homeostasis [6,[76][77][78][79][80][81][82][83][84][85], cancer [6,80,81,84,[86][87][88][89], energy metabolism and aging [70,74,77,84,90], mitochondrial energy maintenance [76,81,91,92], renal disease [78,86], and viral diseases [72,[93][94][95][96][97][98][99][100][101]. Circadian rhythm in mammals is controlled in a region over the optic chiasm that detects light with retinal photosensitive ganglion cells in the suprachiasmatic nucleus (SCN) [6,84,98]. With the exposure to external light, biological clock genes oversee biochemical cell transmissions, physiological process in the body, and changes in behavior.…”

Electrochemical Sensors Based on Carbon Nanomaterial Used in Diagnosing Metabolic Disease

“…Metabolic diseases are usually caused by metabolic problems, including metabolic disorders and metabolic exuberance (Cani, 2019 ; Sanna et al, 2019 ). Metabolic diseases mainly include diabetes mellitus (DM) (Maiese, 2020 ), non-alcoholic fatty liver disease (NAFLD) (Colca, 2020 ), gout (Oh et al, 2019 ), vitamin deficiency (Kim et al, 2015 ), diabetic ketoacidosis (Musso et al, 2019 ), and other diseases which can also lead to a variety of complications. The metabolic disease will further cause atherosclerosis and other cardiovascular diseases if the patient is not treated in time.…”