Natural products from traditional medicine constitute a large promising pool for compounds that regulate ABCA1 expression, and thus may prevent/treat diseases related to cholesterol metabolism, like atherosclerosis or Alzheimer's disease.
Bexarotene, an agonist of retinoid X receptor alpha (RXRα), has been shown to increase the expression of apoE, ABCA1, and ABCG1 by activating RXR/LXR and RXR/PPAR heterodimers, resulting in amyloid β (Aβ)-protein clearance in the brain of an Alzheimer's disease (AD) mouse model and reversal of mouse cognitive deficits.
Enhancing ABCA1 activity to reduce ApoE and ABCA1 aggregation is a potential therapeutic strategy for the prevention of ApoE4 aggregation-driven pathology.<b>SIGNIFICANCE STATEMENT</b> ApoE protein plays a key role in the formation of amyloid plaques, a hallmark of Alzheimer's disease (AD).
Therefore, aerobic training by a significant increase in the mRNA expression of ABCA1, which is the main factors of lipid metabolism in the brain and which is involved in the pathology of Alzheimer's disease, can be consistent with improving cognitive function as an effective way of preventing and improving the symptoms of Alzheimer's disease.
Collectively, though further studies are needed to probe its effects in vivo, OS could be a potential therapeutic drug for AD by modulating poE metabolism through the LXR-ABCA1 pathway.
Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment.
Altogether, the results are suggesting that treatment of APP/E4/Abca1+/- mice with LXR agonist T0 ameliorates APOE4-induced AD-like pathology and therefore targeting the LXR-ABCA1-APOE regulatory axis could be effective as a potential therapeutic approach in AD patients, carriers of APOEε4.
Moreover, TP70 was able to reduce oxidative stress, inhibit acyl-coenzyme A:cholesterol acyltransferase (ACAT), and upregulate the expression of ATP-binding cassette subfamily A, member 1 (ABCA1), actions considered neuroprotective in AD.
Interestingly, the difference between the healthy subjects and the MCI and mAD patients with respect to the capacity of HDL to mediate cholesterol efflux disappeared when ATP-binding cassette transporter A1 (ABCA1)-enriched J774 macrophages were used.
ABCA1R219K RR genotype was positively correlated to MMSE value in AD patients, while ABCA1 R219K KK genotype was negatively correlated to H-Y value in PD patients.
ATP-binding cassette transporter 1 (ABCA1) is a cholesterol efflux transporter that when absent increases and when overexpressed reduces brain amyloid-β deposition in mouse models of Alzheimer's disease.
In addition, ABCA1rs2066718 and rs1800977 polymorphisms might not contribute to AD susceptibility in general population, but they should play a role on AD development when interacted with ApoE-ε4.
Common Pesticide, Dichlorodiphenyltrichloroethane (DDT), Increases Amyloid-β Levels by Impairing the Function of ABCA1 and IDE: Implication for Alzheimer's Disease.
A loss-of-function mutation in ABCA1, present in 1:500 individuals, was associated with low plasma levels of apoE and with high risk of AD and cerebrovascular disease in the general population.
Previous data demonstrate that bexarotene (Bex), retinoid X receptor (RXR) agonist, reduces soluble and insoluble amyloid-β (Aβ) in Alzheimer disease (AD)-transgenic mice either by increasing the levels of mouse apolipoprotein E (apoE) or increasing ABCA1/ABCG1-induced apoE lipoprotein association/lipidation.