Investigation of the role of BACE1 in adipocyte and immune cell function
type: CreativeWork
description: Metabolic disorders, including obesity and type 2 diabetes (T2D), place a huge health and economic burden on society with the National Health Service (NHS) becoming increasingly overwhelmed. Moreover, metabolic disorders often manifest with numerous co-morbidities that include cardiovascular disease (CVD), various cancers and Alzheimer’s disease (AD), exacerbating the problem. Therefore research into metabolic dysregulation and its associated conditions is vital for the future treatment of these disorders and so to relieve the social and financial burdens. AD commonly co-manifests alongside metabolic diseases and this neurodegenerative condition is hugely prevalent in the aging population of today. One of the major pathologies, which many believe to be causative, associated with AD is amyloid plaque formation. Amyloid plaques occur as an aggregated form of amyloid peptides whose formation is dependent upon cleavage by an aspartyl protease named BACE1 (β-site amyloid precursor protein cleaving enzyme 1). This enzyme is the rate-limiting enzyme involved in the cleavage of amyloid precursor protein (APP) which, followed by γ-secretase cleavage, results in amyloid (or Aβ) peptide formation leading to amyloid plaques. BACE1 has also recently been implicated in metabolism with the discovery that BACE1 KO mice are protected against diet-induced obesity (DIO) and its associated diabetes. These findings were supported by use of BACE1 inhibitors in obese mice which mimicked the knock-out studies and subsequently were found to modulate energy homeostasis both in vivo and in vitro. In addition to an improved metabolic phenotype BACE1 KO mice exhibited protection against the chronic inflammation commonly linked to obesity. This was shown by a reduction in immune cell infiltration, in particular macrophages, in the white adipose tissue (WAT) and liver accompanied by reduced levels of pro-inflammatory, and increased levels of anti-inflammatory, cytokines within the WAT. This led t…
abstract: Metabolic disorders, including obesity and type 2 diabetes (T2D), place a huge health and economic burden on society with the National Health Service (NHS) becoming increasingly overwhelmed. Moreover, metabolic disorders often manifest with numerous co-morbidities that include cardiovascular disease (CVD), various cancers and Alzheimer’s disease (AD), exacerbating the problem. Therefore research into metabolic dysregulation and its associated conditions is vital for the future treatment of these disorders and so to relieve the social and financial burdens. AD commonly co-manifests alongside metabolic diseases and this neurodegenerative condition is hugely prevalent in the aging population of today. One of the major pathologies, which many believe to be causative, associated with AD is amyloid plaque formation. Amyloid plaques occur as an aggregated form of amyloid peptides whose formation is dependent upon cleavage by an aspartyl protease named BACE1 (β-site amyloid precursor protein cleaving enzyme 1). This enzyme is the rate-limiting enzyme involved in the cleavage of amyloid precursor protein (APP) which, followed by γ-secretase cleavage, results in amyloid (or Aβ) peptide formation leading to amyloid plaques. BACE1 has also recently been implicated in metabolism with the discovery that BACE1 KO mice are protected against diet-induced obesity (DIO) and its associated diabetes. These findings were supported by use of BACE1 inhibitors in obese mice which mimicked the knock-out studies and subsequently were found to modulate energy homeostasis both in vivo and in vitro. In addition to an improved metabolic phenotype BACE1 KO mice exhibited protection against the chronic inflammation commonly linked to obesity. This was shown by a reduction in immune cell infiltration, in particular macrophages, in the white adipose tissue (WAT) and liver accompanied by reduced levels of pro-inflammatory, and increased levels of anti-inflammatory, cytokines within the WAT. This led t…
author: Cavellini, Daniella L.
language: eng
date published: 2019
date modified: 2026-07-24T02:08:46Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee