Crosstalk between neurological, cardiovascular, and lifestyle disorders: insulin and lipoproteins in the lead role.

Abstract

Insulin resistance and impaired lipoprotein metabolism contribute to a plethora of metabolic and cardiovascular disorders. These alterations have been extensively linked with poor lifestyle choices, such as consumption of a high-fat diet, smoking, stress, and a redundant lifestyle. Moreover, these are also known to increase the co-morbidity of diseases like Type 2 diabetes mellitus and atherosclerosis. Under normal physiological conditions, insulin and lipoproteins exert a neuroprotective role in the central nervous system. However, the tripping of balance between the periphery and center may alter the normal functioning of the brain and lead to neurological disorders such as Alzheimer's disease, Parkinson's disease, stroke, depression, and multiple sclerosis. These neurological disorders are further characterized by certain behavioral and molecular changes that show consistent overlap with alteration in insulin and lipoprotein signaling pathways. Therefore, targeting these two mechanisms not only reveals a way to manage the co-morbidities associated with the circle of the metabolic, central nervous system, and cardiovascular disorders but also exclusively work as a disease-modifying therapy for neurological disorders. In this review, we summarize the role of insulin resistance and lipoproteins in the progression of various neurological conditions and discuss the therapeutic options currently in the clinical pipeline targeting these two mechanisms; in addition, challenges faced in designing these therapeutic approaches have also been touched upon briefly.