The knowledge regarding pathological and treatment resistance mechanisms involved in the pathology of complex brain disorders is far from understood. The neuroinflammation hypothesis of psychiatric, neurological, and neurodegenerative diseases is well-acknowledged. However, this hypothesis is far from understood. Toll-like receptors (TLRs) family is an innate immunity molecule implicated in neuroinflammation in complex brain disorders. This chapter reviews considerable evidence indicating that activation of endotoxins such as lipopolysaccharide is a common factor. Additionally, we report clinical and preclinical studies highlighting the link between lipopolysaccharide, TLRs, and different types of brain disorders. Also, we review the current pharmacological modulations of TLRs. Hoping we would help in filling our knowledge gaps and highlight potential links to tackle new angles in managing complex brain disorders. This chapter’s primary goal is to encourage scientists and researchers to conduct future studies characterizing the nature of endotoxin activation of TLRs in complex brain disorders, filling our knowledge gaps, and finding new treatment strategies.
Part of the book: Therapy Approaches in Neurological Disorders
Our knowledge regarding pathological and treatment resistance mechanisms involved in depression is far from understood. Sexual dimorphism in this topic is well acknowledged. However, the need to highlight sex-based discrepancies is unmet. Ketamine, the dissociative anesthetic, has emerged as a rapid antidepressant. This chapter reviewed sexual dimorphism in pharmacological and genetic models of depression, emphasizing ketamine-related antidepressant effects. Aiming by this report, we would extend our knowledge, highlight gender as one of the vital factors in examining depression in preclinical studies, and elucidate complex antidepressant effects associated with ketamine administration. Our central goal is to encourage neuroscientists to consider gender in their studies of mood disorders.
Part of the book: Ketamine Revisited
G protein-coupled receptor kinases (GRKs), the negative regulators of G protein-coupled receptors (GPCRs), have a key role in cardiovascular disease pathophysiology. Alteration in GRKs’ expressions and/or kinase activity has been reported in preclinical animal models as well as in patients with cardiovascular diseases. This alteration might be a contributing factor to disease progression by a variety of mechanisms such as non-canonical transduction pathways. The current chapter is aimed to expand our knowledge and understanding of the function of GRKs in cardiovascular diseases, highlight their involvement, and illustrate the possible mechanistic role of GRKs in hypertensive vascular diseases and cardiac myopathy. The current chapter also is endeavoured to identify the potential molecular mechanisms by which GRKs participate in cardiovascular disease progression. Building the basics knowledge about GRKs in cardiovascular diseases will help to assess the potential utilization of GRKs as therapeutic targets and to examine the possible approaches to modulate their protein expression or to inhibit their kinase activity to prevent or attenuate cardiovascular disease progression.
Part of the book: Cardiovascular Diseases