Drugs and drug delivery systems targeting amyloid-β in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure and limited treatment solutions that are unable to target any of the suspected causes. Increasing evidence suggests that one of the causes of neurodegeneration is the overproduction of amyloid beta (Aβ) and the inability of Aβ peptides to be cleared from the brain, resulting in self-aggregation to form toxic oligomers, fibrils and plaques. One of the potential treatment options is to target Aβ and prevent self-aggregation to allow for a natural clearing of the brain. In this paper, we review the drugs and drug delivery systems that target Aβ in relation to Alzheimer's disease. Many attempts have been made to use anti-Aβ targeting molecules capable of targeting Aβ (with much success in vitro and in vivo animal models), but the major obstacle to this technique is the challenge posed by the blood brain barrier (BBB). This highly selective barrier protects the brain from toxic molecules and pathogens and prevents the delivery of most drugs. Therefore novel Aβ aggregation inhibitor drugs will require well thought-out drug delivery systems to deliver sufficient concentrations to the brain.

Cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and antagonist for amylin fibrillation

“…S4). Remarkably, an increase in the concentration of PMAQA resulted in a substantial line broadening, and loss of 15 N/ 1 H resonances of Aβ40 were observed at 3 µM PMAQA (Fig. S3).…”

“…But the poor solubility and bioavailability affect their therapeutic nature and recently have been shown to be overcome using nanocarriers. [13][14][15] Although, their mechanism of action remains unknown, hydrogen bonding, hydrophobic interactions and π-π stacking are thought to be the major driving forces for their inhibitory mechanism of action. 16,17 Despite substantial efforts, no significant new drugs have been discovered against these most tenacious and unnerving medical disorders.…”

Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases

“…Increasing research investigation indicates that the overproduction of amyloid beta (Ab) and incapacity of Ab peptides to be cleared from the brain is one of the causes of degeneration of nervous system. The cumulative deposition of this protein results in self-aggregation to form toxic oligomers, neurofibrillary plaques, and tangles [161]. The plagues are made by single molecules of Ab cluster.…”

Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

“…There are several theories related to AD pathophysiology, among which the amyloid cascade hypothesis is the most relevant and accepted one, which states that the neurologic degeneration occurs as a result of the formation and accumulation of toxic, soluble amyloid beta (Aβ) oligomers, which are formed by the misfolding of Aβ monomers [ 13 ]. These monomeric entities are formed by β- and γ-secretase-mediated amyloid precursor protein (APP) cleavage [ 14 ], and contribute to the development of larger fibrils and plaque.…”