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   Normal and Pathological NRF2 Signalling in the Central Nervous SystemHeurtaux, Tony  ; ; et alin Antioxidants (2022), 11(8), 1426 The nuclear factor erythroid 2-related factor 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions ... [more ▼] The nuclear factor erythroid 2-related factor 2 (NRF2) was originally described as a master regulator of antioxidant cellular response, but in the time since, numerous important biological functions linked to cell survival, cellular detoxification, metabolism, autophagy, proteostasis, inflammation, immunity, and differentiation have been attributed to this pleiotropic transcription factor that regulates hundreds of genes. After 40 years of in-depth research and key discoveries, NRF2 is now at the center of a vast regulatory network, revealing NRF2 signalling as increasingly complex. It is widely recognized that reactive oxygen species (ROS) play a key role in human physiological and pathological processes such as ageing, obesity, diabetes, cancer, and neurodegenerative diseases. The high oxygen consumption associated with high levels of free iron and oxidizable unsaturated lipids make the brain particularly vulnerable to oxidative stress. A good stability of NRF2 activity is thus crucial to maintain the redox balance and therefore brain homeostasis. In this review, we have gathered recent data about the contribution of the NRF2 pathway in the healthy brain as well as during metabolic diseases, cancer, ageing, and ageing-related neurodegenerative diseases. We also discuss promising therapeutic strategies and the need for better understanding of cell-type-specific functions of NRF2 in these different fields. [less ▲] Detailed reference viewed: 145 (9 UL)Microgliosis: a double-edged sword in the control of food intake; ; et al in FEBS Journal (2022) Maintaining energy balance is essential for survival and health. This physiological function is controlled by the brain, which adapts food intake to energy needs. Indeed, the brain constantly receives a ... [more ▼] Maintaining energy balance is essential for survival and health. This physiological function is controlled by the brain, which adapts food intake to energy needs. Indeed, the brain constantly receives a multitude of biological signals that are derived from digested foods or that originate from the gastrointestinal tract, energy stores (liver and adipose tissues) and other metabolically active organs (muscles). These signals, which include circulating nutrients, hormones and neuronal inputs from the periphery, collectively provide information on the overall energy status of the body. In the brain, several neuronal populations can specifically detect these signals. Nutrient-sensing neurons are found in discrete brain areas and are highly enriched in the hypothalamus. In turn, specialized brain circuits coordinate homeostatic responses acting mainly on appetite, peripheral metabolism, activity and arousal. Accumulating evidence shows that hypothalamic microglial cells located at the vicinity of these circuits can influence the brain control of energy balance. However, microglial cells could have opposite effects on energy balance, that is homeostatic or detrimental, and the conditions for this shift are not totally understood yet. One hypothesis relies on the extent of microglial activation, and nutritional lipids can considerably change it. [less ▲] Detailed reference viewed: 142 (0 UL)Postprandial hyperglycemia stimulates neuroglial plasticity in hypothalamic POMC neurons after a balanced meal; ; et al in Cell Reports (2020), 30 Detailed reference viewed: 194 (5 UL) |
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