Nontoxic amphiphilic carbon dots as promising drug nanocarriers across the blood–brain barrier and inhibitors of β-amyloid

Nanoscale ◽  
2019 ◽  
Vol 11 (46) ◽  
pp. 22387-22397 ◽  
Author(s):  
Yiqun Zhou ◽  
Piumi Y. Liyanage ◽  
Dinesh Devadoss ◽  
Linda Rebeca Rios Guevara ◽  
Ling Cheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Carbon Dots ◽  
Brain Barrier ◽  
Blood Brain ◽  
Β Amyloid ◽  
Amyloid P ◽  
Drug Nanocarriers

Unique nontoxic amphiphilic carbon dots have been developed as an excellent drug nanocarrier targeting the Alzheimer's disease by crossing the blood-brain barrier (BBB) while inhibiting the production of β-amyloid.

scholarly journals BACE-1 is expressed in the blood–brain barrier endothelium and is upregulated in a murine model of Alzheimer’s disease

2015 ◽  
Vol 36 (7) ◽  
pp. 1281-1294 ◽  
Author(s):  
Kavi Devraj ◽  
Slobodan Poznanovic ◽  
Christoph Spahn ◽  
Gerhard Schwall ◽  
Patrick N Harter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mouse Brain Endothelial Cells ◽  
Primary Mouse ◽  
Β Amyloid ◽  
Bace 1

Endothelial cells of the blood–brain barrier form a structural and functional barrier maintaining brain homeostasis via paracellular tight junctions and specific transporters such as P-glycoprotein. The blood–brain barrier is responsible for negligible bioavailability of many neuroprotective drugs. In Alzheimer’s disease, current treatment approaches include inhibitors of BACE-1 (β-site of amyloid precursor protein cleaving enzyme), a proteinase generating neurotoxic β-amyloid. It is known that BACE-1 is highly expressed in endosomes and membranes of neurons and glia. We now provide evidence that BACE-1 is expressed in blood–brain barrier endothelial cells of human, mouse, and bovine origin. We further show its predominant membrane localization by 3D- dSTORM super-resolution microscopy, and by biochemical fractionation that further shows an abluminal distribution of BACE-1 in brain microvessels. We confirm its functionality in processing APP in primary mouse brain endothelial cells. In an Alzheimer’s disease mouse model we show that BACE-1 is upregulated at the blood–brain barrier compared to healthy controls. We therefore suggest a critical role for BACE-1 at the blood–brain barrier in β-amyloid generation and in vascular aspects of Alzheimer’s disease, particularly in the development of cerebral amyloid angiopathy.

Design and synthesis of novel tacrine–indole hybrids as potential multitarget-directed ligands for the treatment of Alzheimer's disease

2021 ◽  
Author(s):  
Slavka Hamulakova ◽  
Zuzana Kudlickova ◽  
Ladislav Janovec ◽  
Roman Mezencev ◽  
Zachery J Deckner ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Acetylcholinesterase Inhibitors ◽  
Biological Evaluation ◽  
Brain Barrier ◽  
Amyloid Formation ◽  
Design And Synthesis ◽  
Blood Brain ◽  
Β Amyloid

The authors report on the synthesis and biological evaluation of new compounds whose structure combines tacrine and indole moieties. Tacrine–indole heterodimers were designed to inhibit cholinesterases and β-amyloid formation, and to cross the blood–brain barrier. The most potent new acetylcholinesterase inhibitors were compounds 3c and 4d (IC50 = 25 and 39 nM, respectively). Compound 3c displayed considerably higher selectivity for acetylcholinesterase relative to human plasma butyrylcholinesterase in comparison to compound 4d (selectivity index: IC50 [butyrylcholinesterase]/IC50 [acetylcholinesterase] = 3 and 0.6, respectively). Furthermore, compound 3c inhibited β-amyloid-dependent amyloid nucleation in the yeast-based prion nucleation assay and displayed no dsDNA destabilizing interactions with DNA. Compounds 3c and 4d displayed a high probability of crossing the blood–brain barrier. The results support the potential of 3c for future development as a dual-acting therapeutic agent in the prevention and/or treatment of Alzheimer's disease.

scholarly journals A first-principles study on potential chelation agents and indicators of Alzheimer's disease

RSC Advances ◽  
2020 ◽  
Vol 10 (58) ◽  
pp. 35574-35581
Author(s):  
Bryan Wang ◽  
Xuan Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Serum ◽  
Blood Brain Barrier ◽  
First Principles ◽  
Brain Barrier ◽  
Serum Transferrin ◽  
Human Serum Transferrin ◽  
First Principles Study ◽  
Blood Brain

Human-serum transferrin is involved in the transportation of aluminum across the blood–brain barrier.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

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