Year: 2019
Type: dissertation
Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative pathology characterized by synaptic impairment and the loss of neurons in some subcortical areas, which afterwards leads to dementia. This occurs primarily due the excessive accumulation and deposition of β-amyloid peptide (Aβ) in the form of plaques, and the generation of neurofibrillary tangles. Considering the studies suggesting the appearance of amyloid plaques occurs before neurofibrillary tangles and taking into account that the familiar form of AD (FAD) is associated, among others, with an APP gene mutation leading to the overproduction of Aβ, the inhibition of Aβ production as the potential to be a disease-modifying therapy. Based in this hypothesis, BACE1, or β-secretase, has been considered a prime target in the development of new therapies to Alzheimer's disease.Many efforts have been made to develop small BACE1 inhibitors as drugs for AD and, although various inhibitors have been described, few had presented a balance between the in vitro potency and the necessary pharmaco-kinetic properties to achieve in vivo effectiveness.Asiatic acid is a well-studied compound with therapeutic potential in many different pathologies including neurodegenerative diseases. A recent study showed that the neuroprotective effect of this compound is associated with the down-regulation of BACE1 protein levels making this molecule a good candidate to study in this work.In order to prepare BACE1 inhibitor candidates, this work focused on the synthesis of new fluorinated asiatic acid derivatives, as well as their structural elucidation by spectral analysis.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2965325090