Abstract
Neurodegenerative disease is an umbrella term for different conditions which primarily affect the neurons in the human brain. In the last century, significant research has been focused on mechanisms and risk factors relevant to the multifaceted etiopathogenesis of neurodegenerative diseases. Currently, neurodegenerative diseases are incurable, and the treatments available only control the symptoms or delay the progression of the disease. This review is aimed at characterizing the complex network of molecular mechanisms underpinning acute and chronic neurodegeneration, focusing on the disturbance in redox homeostasis, as a common mechanism behind five pivotal risk factors: aging, oxidative stress, inflammation, glycation, and vascular injury. Considering the complex multifactorial nature of neurodegenerative diseases, a preventive strategy able to simultaneously target multiple risk factors and disease mechanisms at an early stage is most likely to be effective to slow/halt the progression of neurodegenerative diseases.
Highlights
Neurodegenerative diseases define diversified chronic disorders related to the progressive motor, sensory, and perceptual dysfunctions which lead to cognitive and behavioural deficits
This is probably due to the functional changes that happened in the blood-brain barrier (BBB) as a result of brain injury, including decreased trafficking of peripheral immune cells into the brain parenchyma and increased oxidative stress and inflammatory mediator release that lead to an amplification of the inflammatory response in the injured brain [105]
Associated with Endothelial Cell Dysfunction. Vascular risk factors such as age, diabetes, hypertension, and hypercholesterolemia often overlap with neurodegenerative risk factors in older patients, and vascular dysfunction is recognized as a determinant in several neurodegenerative diseases such as Alzheimer’s disease (AD), cerebral amyloid angiopathy (CAA), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [160,161,162,163]
Summary
Neurodegenerative diseases define diversified chronic disorders related to the progressive motor, sensory, and perceptual dysfunctions which lead to cognitive and behavioural deficits In these pathologies, the selective neuronal cell loss appears in the adulthood, within different areas of the brain [1]. Small molecules, become available, are able to interact with specific targets and useful for therapeutic proof-of-concept studies In this view, the importance of investigating the complex interrelated molecular mechanisms behind neurodegenerative disease onset and progression appear undeniable. In an attempt to characterize the complex network of molecular mechanisms underpinning acute and chronic neurodegeneration, this review is focused on the disturbance in redox homeostasis, as common mechanism behind five pivotal risk factors: aging, oxidative stress, inflammation, vascular injury, and glycation
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