Editorial: Metabolic signaling dysregulation and cognitive impairments in aging and Alzheimer's disease, volume II

Regulation of energy metabolism homeostasis is an essential biological process that is critical for function and survival of all organisms. Metabolism involves numerous fuel sources and pathways that can be generally divided into two categories: the anabolic pathway which consumes energy and includes biosynthesis of molecules such proteins and lipids; and the catabolic pathway which releases energy and involves breakdown of complex molecules. The energy demands and metabolic rate of the brain are significant: with < 2% of the body weight, the brain consumes more than 20% of the body energy (Shulman et al., 2004; Hyder et al., 2013; Watts et al., 2018). Thus, the brain is uniquely susceptible to changes in energy availability and utilization, all of which put the brain at risk for damage or disease. Notably, dysregulation of energy metabolism and related signaling pathways in the nervous and other body systems are linked to synaptic failure and cognitive impairments in many aging-related CNS disorders including AD, Parkinson's disease, and mild cognitive impairment (MCI) (Lin and Beal, 2006; Arnold et al., 2018; Carroll and Macauley, 2019; Ryu et al., 2019; Wang et al., 2019; Wilkins and Swerdlow, 2021). Moreover, emerging evidence suggests that alterations in brain metabolism are not only related to neuronal injury but also changes in glial and vascular function associated with CNS disorders (Shippy and Ulland, 2020; Xiang et al., 2021; Ardanaz et al., 2022; Salvadó et al., 2022). Therefore, understanding the physiological and pathological roles of various metabolic processes and related signaling cascades in cognition may provide important insights into development of novel therapeutic targets and prognostic/diagnostic biomarkers for AD and related dementias (ADRDs).