Curcumin and Novel Synthetic Analogs in Cell-Based Studies of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is associated with the most common type of dementia and is characterized by the presence of deposits of the protein fragment amyloid beta (Aβ) in the brain. The natural product mixture of curcuminoids that improves certain defects in innate immune cells of AD patients may selectively enhance Aβ phagocytosis by alteration of gene transcription. In this work, we evaluated the protective effects of curcuminoids in cells from AD patients by investigating the effect on NF-κB and BACE1 signaling pathways. These results were compared to the gene expression profile of the clearance of Aβ. The minor curcumin constituent, bisdemethoxycurcumin (BDC) showed the most potent protective action to decrease levels of NF-κB and BACE1, decrease the inflammatory cascade and diminish Aβ aggregates in cells from AD patients. Moreover, mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (MGAT3) and vitamin D receptor (VDR) gene mRNAs were up-regulated in peripheral blood mononuclear cells from AD patients treated with BDC. BDC treatment impacts both gene expression including Mannosyl (Beta-1,4-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Vitamin D and Toll like receptor mRNA and Aβ phagocytosis. The observation of down-regulation of BACE1 and NF-κB following administration of BDC to cells from AD patients as a model system may have utility in the treatment of asymptomatic AD patients.

Alzheimer’s, Parkinson’s Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement

“…In this paper, we report a whole transcriptome profiling of both long non-coding and coding RNAs in peripheral blood mononuclear cells (PBMCs) of unmutated SALS) patients [ 24 ], unmutated sporadic AD patients, unmutated sporadic PD patients, and matched controls. PBMCs were chosen as they have been reported to be source of protein and nucleic acid biomarkers in neurodegenerative disorders, also allowing for their use as cellular models for these diseases [ 24 , 25 , 26 , 27 ]. After transcriptome analysis, we focused on the identification of possible crossroads or deviations in the dysregulated pathways of AD, PD, and ALS.…”

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

“…Etherification of the hydroxyl groups, on both aromatic rings, showed a higher anti-inflammatory activity. Gagliardi et al [80] showed that treatment with curcuminoids, in a cell model PBMC (peripheral blood mononuclear cells, Supplementary Data), inhibited the activation of inflammation. AB14 showed the most potent protective activity decreasing levels of NF-κB and BACE1 and the inflammatory cascade in cells from AD patients (Figure 1).…”

Can Brain Health Be Supported by Vitamin D-Based Supplements? A Critical Review

“…The results of many studies may be relevant to the use of curcuminoids and vitamin D3 in the prevention of neurodegenerative diseases, which are substances that work via antioxidant and anti-inflammatory mechanisms ([ 179 ] Figure 1 ). Indeed, morbidities of aging have been related to defective functions of both T cells and macrophages leading to brain amyloidosis and inflammation [ 180 ].…”

“…“Inflammaging” may be associated with an increase in incompetent memory T cells and inflammatory cytokines produced by macrophages, whereas the defective clearance of amyloid-beta Aβ1–42 may be related to the defective transcription of immune genes necessary for phagocytosis, β-1,4-mannosyl-glycoprotein, 4-β-N-acetylglucosaminyltransferase, and Toll-like receptors. The approaches used for re-balancing Aβ immunity and inflammation are being pursued in animal models and the peripheral blood mononuclear cells of patients [ 179 , 181 , 182 , 183 ]. Increased inflammation may represent the “first hit” and defective transcription of immune genes represent the “second hit” in the pathogenesis of AD.…”

“…Gagliardo et al conducted studies that showed that treatment with curcumin may decrease the predisposition of Aβ to accumulate in cells. Although the role of Aβ 1-42 as a potential causative agent in the pathophysiology of neurodegenerative disease has been documented extensively, the exact molecular mechanisms and their biochemical effect on brain tissues are not very clear [ 179 , 183 ]. An in vitro experiment by Alamro et al on primary neuronal cultures investigated the effect of Aβ 1-42 on the primary neuronal cells and the role of vitamin D3 or curcumin used as a natural therapy for AD treatment.…”