The Blood Brain Barrier and its Role in Alzheimer's Therapy: An Overview

Abstract

In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients.

Pharmacotechnical Development of a Nasal Drug Delivery Composite Nanosystem Intended for Alzheimer’s Disease Treatment

“…AD and other types of neurodegenerative diseases are difficult to treat in particular because of the blood-brain barrier (BBB). As BBB restricts transport of drugs to the brain, very few drugs are actually available for treatment of AD [5]. While preventing the neurotoxic xenobiotics' access into the central nervous system (CNS) to protect it, it also strongly limits the administration of neuroprotective drugs to the CNS.…”

Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET radioligands for imaging of Alzheimer’s disease

“…The crude product was purified by silica gel column chromatography with CH 2 Cl 2 /MeOH (200:1 to 20:1) as eluent to afford 5a as a white solid (3.9g, 89.7%), mp 136.9-138.7 ºC. 1…”

Gastrointestinal (GI) Tract Microbes and Microbial Neurotoxins in the Human Central Nervous System (CNS) in Alzheimer’s Disease (AD)

“…This agerelated increase in permeability appears to make the normally protected CNS compartments more exposed and potentially susceptible to neurotoxins generated by dietary and/or environmental pathogens and GI tract-resident microbes normally contained within the GI compartment [10,11,62]. Moreover (i) dietary, environmental and pathological infections, including chronic bacterial or viral influences, or disease-related toxins such as LPS, sncRNA and the 42-amino acid amyloid beta (Aβ42) peptide can progressively and permanently alter blood-brain barrier permeability and thereby facilitate cerebral vascular dysfunction and cerebral colonization by opportunistic microbes as we age [11,63]; and (ii) microbial dysbiosis in the GI tract microbiome can induce inflammatory signaling detrimental to both GI tract and BBB dysfunction that is associated with the pathogenesis of obesity, type 2 diabetes and AD [11,22,64]. Indeed, one major contributing factor to AD pathogenesis is cerebral vascular dysfunction due in part to the loss of the protective function of the BBB and impaired clearance of excess neurotoxic Aβ peptides that induce perivascular association with amyloid peptides, vascular perturbation and altered neurovascular function [63,64].…”

“…Moreover (i) dietary, environmental and pathological infections, including chronic bacterial or viral influences, or disease-related toxins such as LPS, sncRNA and the 42-amino acid amyloid beta (Aβ42) peptide can progressively and permanently alter blood-brain barrier permeability and thereby facilitate cerebral vascular dysfunction and cerebral colonization by opportunistic microbes as we age [11,63]; and (ii) microbial dysbiosis in the GI tract microbiome can induce inflammatory signaling detrimental to both GI tract and BBB dysfunction that is associated with the pathogenesis of obesity, type 2 diabetes and AD [11,22,64]. Indeed, one major contributing factor to AD pathogenesis is cerebral vascular dysfunction due in part to the loss of the protective function of the BBB and impaired clearance of excess neurotoxic Aβ peptides that induce perivascular association with amyloid peptides, vascular perturbation and altered neurovascular function [63,64]. The relationship between the prevalence of AD and vascular permeability factors along the microbiota-GI-tract-CNS axis as a bidirectional communication system that also includes the supplementary influences of neural, immune, endocrine, and metabolic pathways is exceedingly complex and currently not fully understood.…”

“…The relationship between the prevalence of AD and vascular permeability factors along the microbiota-GI-tract-CNS axis as a bidirectional communication system that also includes the supplementary influences of neural, immune, endocrine, and metabolic pathways is exceedingly complex and currently not fully understood. A more complete understanding of the underlying mechanisms that maintain GI tract and BBB homeostasis should provide novel mechanistic insights and more efficacious therapeutic strategies ultimately useful in the clinical management of AD [11,63,64].…”