Metabolic syndrome (MetS), a large public health outlay worldwide, is a cluster of cardiometabolic risk factors highly prevalent in adults. It is defined by at least three of: fasting hyperglycemia/insulin resistance, hypertriglyceridemia, low HDL-cholesterol, visceral obesity, and hypertension. Atherogenic dyslipidemia, oxidative stress, neuroinflammation, and a generalized prothrombotic/proinflammatory state characterize MetS, leading to chronic cerebral hypoperfusion and neurodegeneration and favoring neurological and psychiatric conditions. Alzheimer’s disease and other dementias, diabetes, and stroke are among the ten top leading causes of death globally. MetS affects nearly 30% of the world population, with a 2-3-fold increase in morbidity and mortality. Insulin resistance is key in MetS pathogenesis, associated with cognitive decline, abnormal visuospatial function, poor attention, and slowed psychomotor behavior. Alzheimer’s disease is also named brain diabetes due to shared pathogenic mechanisms. Vice versa, amyloid aggregation, and deposition favor diabetes pathology.
This work addresses neurological comorbidity in MetS to foresee putative new therapeutic targets and biomarkers development. Identifying, designing, or developing therapeutic strategies to improve the metabolic-neurological connection will reduce MetS’ neurological impact. Recent advances report amyloid-ß aggregates in diabetes and pancreatic islet amyloid polypeptide in AD, regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, overlapped with molecular, biochemical, pathophysiological, and metabolic imbalance typical of MetS. Insulin resistance leads to oxidative stress, neuroinflammation, amyloid-beta deposition, and aberrant tau phosphorylation. Dysregulated insulin/IGF-1 signaling accelerates brain aging, affects neuroplasticity, and explains neuroinflammation, astrogliosis, loss of myelinated fibrils, leukoaraiosis, loss of synapses, dystrophic neurites’ growth, and non-amyloid-beta microvascular disease. There are two major insulin signal transduction pathways, the PBK/AKT pathway (metabolic effects) and the MAPK pathway (cell growth, survival, and gene expression). Neurodegenerative dementia shows synaptic, and neuronal loss, microgliosis, impaired glucose metabolism, and insulin-phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)-Akt signaling in the brain. Brain insulin is key to regulating cognitive functions, particularly memory. Defective brain insulin signaling may contribute to neurodegenerative disorders. MetS-associated hypercoagulability with low fibrinolytic activity and high blood viscosity promotes microthrombi formation.
We welcome papers covering, but not restricted to:
•The relationship of metabolic syndrome and insulin signaling with neurological conditions, including but not limited to neuroinflammation, oxidative stress, microglial activation, chronic brain hypoperfusion, increased brain-blood barrier permeability, amyloid aggregation, mild cognitive impairment, Alzheimer's disease/other dementias, Parkinson's disease, cerebrovascular disease, etc.
• Metabolic syndrome, leukoaraiosis in young people, and age-related dementia.
• Insulin, ghrelin, systemic inflammation, and neurodegeneration/neurovascular damage.
• The metabolic-cognitive syndrome, a new entity.
Metabolic syndrome (MetS), a large public health outlay worldwide, is a cluster of cardiometabolic risk factors highly prevalent in adults. It is defined by at least three of: fasting hyperglycemia/insulin resistance, hypertriglyceridemia, low HDL-cholesterol, visceral obesity, and hypertension. Atherogenic dyslipidemia, oxidative stress, neuroinflammation, and a generalized prothrombotic/proinflammatory state characterize MetS, leading to chronic cerebral hypoperfusion and neurodegeneration and favoring neurological and psychiatric conditions. Alzheimer’s disease and other dementias, diabetes, and stroke are among the ten top leading causes of death globally. MetS affects nearly 30% of the world population, with a 2-3-fold increase in morbidity and mortality. Insulin resistance is key in MetS pathogenesis, associated with cognitive decline, abnormal visuospatial function, poor attention, and slowed psychomotor behavior. Alzheimer’s disease is also named brain diabetes due to shared pathogenic mechanisms. Vice versa, amyloid aggregation, and deposition favor diabetes pathology.
This work addresses neurological comorbidity in MetS to foresee putative new therapeutic targets and biomarkers development. Identifying, designing, or developing therapeutic strategies to improve the metabolic-neurological connection will reduce MetS’ neurological impact. Recent advances report amyloid-ß aggregates in diabetes and pancreatic islet amyloid polypeptide in AD, regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, overlapped with molecular, biochemical, pathophysiological, and metabolic imbalance typical of MetS. Insulin resistance leads to oxidative stress, neuroinflammation, amyloid-beta deposition, and aberrant tau phosphorylation. Dysregulated insulin/IGF-1 signaling accelerates brain aging, affects neuroplasticity, and explains neuroinflammation, astrogliosis, loss of myelinated fibrils, leukoaraiosis, loss of synapses, dystrophic neurites’ growth, and non-amyloid-beta microvascular disease. There are two major insulin signal transduction pathways, the PBK/AKT pathway (metabolic effects) and the MAPK pathway (cell growth, survival, and gene expression). Neurodegenerative dementia shows synaptic, and neuronal loss, microgliosis, impaired glucose metabolism, and insulin-phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3)-Akt signaling in the brain. Brain insulin is key to regulating cognitive functions, particularly memory. Defective brain insulin signaling may contribute to neurodegenerative disorders. MetS-associated hypercoagulability with low fibrinolytic activity and high blood viscosity promotes microthrombi formation.
We welcome papers covering, but not restricted to:
•The relationship of metabolic syndrome and insulin signaling with neurological conditions, including but not limited to neuroinflammation, oxidative stress, microglial activation, chronic brain hypoperfusion, increased brain-blood barrier permeability, amyloid aggregation, mild cognitive impairment, Alzheimer's disease/other dementias, Parkinson's disease, cerebrovascular disease, etc.
• Metabolic syndrome, leukoaraiosis in young people, and age-related dementia.
• Insulin, ghrelin, systemic inflammation, and neurodegeneration/neurovascular damage.
• The metabolic-cognitive syndrome, a new entity.
