Cellular processes series#

A relevant issue on the clinical approach to AD and related pathologies that lead to cognitive impairment is the fact that most of the research efforts on therapeutics have focused on either fighting the symptoms by boosting certain deteriorated transmission pathways (e.g., anti-acetylcholinesterase drugs to enhance cholinergic transmission) or reducing Aβ load via immunotherapy. Accordingly, a more detailed in-depth analysis of central insulin resistance contribution to cognitive impairment is discussed later in this review.

Present results suggest that unhealthy dietary habits, microbiota changes, and oxidative stress favor the development of brain insulin resistance, which could contribute to a neuroinflammatory profile, directly activating both the resident immune cells of the brain (microglia) and astrocytes, promoting an adverse environment for neuronal survival in the context of AD. An approach for slowing down the progress of the disease is targeting the factors that might accelerate neural damage. Common features of AD are the aggregation of β-amyloid (Aβ) plaques and tau protein hyperphosphorylation, leading to neural damage. Delaying a cognitive decline in AD is a major research challenge and a clinical need, considering the incidence of this disease in the elderly. AD leads to a loss of memory and neurodegenerative cognitive functions and affects 10% of the population aged over 65 years. By 2050, more than 131.5 million people are expected to be affected. Taking this trend into consideration and the prevalence of dementia, including AD, the World Health Organization estimates that population aging will lead to a dramatic increase in dementia prevalence. Ĭurrently, 16% of the EU population is over 65, and this figure is expected to rise to 25% by 2030. Central insulin resistance is a common feature linked to premature aging and is observed in neurological disorders, including early stages of Alzheimer’s disease (AD) and Down’s syndrome (DS).

Cellular processes series#

In addition to the well-known peripheral role of insulin on glucose and energy storage, insulin also regulates a series of cognitive processes, such as memory formation, through its effects on glial–neuronal metabolic coupling. The dysregulation of the metabolic network leads to an age-related elevated risk of suffering from chronic metabolic disorders, especially insulin resistance-related pathologies. The aging process in humans is associated with physical decline and impairment of metabolic homeostasis. Introduction: Human Brain Aging and Inositols The biomedical uses of inositols may represent a paradigm in the industrial approach perspective, which has generated growing interest for two decades, accompanied by clinical trials for Alzheimer’s disease.ġ.

This work presents a critical review of inositol actions on insulin signaling, oxidative stress, and endothelial dysfunction, and its potential for either preventing or delaying cognitive impairment in aging and neurodegenerative diseases. However, uncertainties of the intrinsic mechanisms of inositols regarding their biology are still unsolved.

Epi- and scyllo-inositol isomers are capable of stabilizing non-toxic forms of β-amyloid proteins, which are characteristic of Alzheimer’s disease and cognitive dementia in Down’s syndrome, both associated with brain insulin resistance. Myo-inositol imbalance is observed in psychiatric diseases and its use shows efficacy for treatment of depression, anxiety, and compulsive disorders.

In the brain, fluctuation of inositols in extracellular and intracellular compartments regulates neuronal and glial activity. Other functions of inositols have been derived from the existence of multiple stereoisomers, which may confer antioxidant properties. Isolation and characterization of inositol phosphoglycans containing myo- or d-chiro-inositol have been milestones for understanding the physiological regulation of insulin signaling. Inositols are sugar-like compounds that are widely distributed in nature and are a part of membrane molecules, participating as second messengers in several cell-signaling processes.