NMR metabolomic investigation of astrocytes interacted with Aβ42 or its complexes with either copper(II) or zinc(II)

Rocchi, Altea; Valensin, Daniela; Aldinucci, Carlo; Giani, Gabriele; Barbucci, Rolando; Gaggelli, Elena; Kozłowski, Henryk; Valensin, Gianni

doi:10.1016/j.jinorgbio.2012.08.021

Cited by 15 publications

(7 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, it is a prevalent method to conjugate metal chelators onto proteins or nanoparticles to increase their biocompatibility and their ability to inhibit metal-associated Aβ aggregation . Among the various proteins/nanoparticles, human serum albumin (HSA) is a natural inhibitor against Aβ aggregation in vivo , and plays an important role in the transportation of metal ions in blood plasma. , Also, HSA has considerable pharmaceutical utility for its physicochemical stability and biocompatibility. − However, the metal-chelate capacity of HSA is very limited, making it unable to deal with the high-concentration metal ions in the brain tissues of AD patients . Hence, we have focused on the use of HSA to develop potent inhibitors of Aβ aggregation.…”

Section: Introductionmentioning

confidence: 71%

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against Metal-Associated Amyloid β-Protein Aggregation and Cytotoxicity

Xie

Zhang

et al. 2017

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Metal-induced amyloid β-protein (Aβ) aggregation plays a key role in the pathogenesis of Alzheimer's disease. Although several agents have been recognized to block metal-associated Aβ aggregation, their therapeutic potential is marred due to the high-concentration metal ions in the amyloid plaques. To overcome this problem, we have herein developed iminodiacetic acid-modified human serum albumin (I-HSA) to fight against the aggregation. The multifunctional nature of I-HSA was extensively characterized in inhibiting the Aβ aggregation associated with Zn and Cu. The results revealed the following: (1) I-HSA significantly inhibited Aβ aggregation and alleviated its cytotoxicity. (2) I-HSA possessed a metal-chelate capacity as high as 31.2 mol/mol, and 25 μM I-HSA could effectively inhibit the influence of 250 μM Zn on Aβ aggregation. (3) Equimolar I-HSA remarkably attenuated the reactive oxygen species damage caused by the Aβ and Cu-Aβ species. (4) I-HSA could remodel metal-Aβ fibrils into unstructured aggregates with less neurotoxicity. The cytotoxicity of mature Cu-Aβ aggregates was mitigated from 64.8% to 25.4% under the functioning of I-HSA. In conclusion, I-HSA showed prominent advantages for the high metal-chelate capacity. To our knowledge, I-HSA is the first multifunctional macromolecule for inhibiting high-concentration metal-induced Aβ aggregation and remodeling mature metal-induced Aβ species.

show abstract

Section: Introductionmentioning

confidence: 71%

Section: ■ Introductionmentioning

confidence: 99%

Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against Metal-Associated Amyloid β-Protein Aggregation and Cytotoxicity

Xie

Zhang

et al. 2017

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Some of these reviews give a general overview on the role of metal ions in general. 233 The deleterious effects of metal ions are often linked to the metal ion catalyzed redox reactions of amyloid peptides. 206 The ultimate goal of these studies is to find the appropriate treatment of AD and the involvement of metal complexes and chelating agents in these studies was also surveyed.…”

Section: Thermodynamic Kinetic and Structural Studies On The Metal Cmentioning

confidence: 99%

Metal complexes of amino acids and peptides

Farkas¹,

Sóvágó²

2014

Amino Acids, Peptides and Proteins

View full text Add to dashboard Cite

show abstract

“…Astrocytes are the most numerous subtypes of glial cell population in the central nervous system (CNS) [ 12 , 13 ]. The roles of astrocytes have been linked to brain development and function such as synapse formation and function, control of neurotransmitters release and uptake, production of trophic factors and control of neuronal survival [ 14 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease

Yoo

Park

Woo

et al. 2020

IJMS

View full text Add to dashboard Cite

Altered glucose metabolism has been implicated in the pathogenesis of Alzheimer’s disease (AD). Aerobic glycolysis from astrocytes is a critical metabolic pathway for brain energy metabolism. Disturbances of circadian rhythm have been associated with AD. While the role of circadian locomotor output cycles kaput (CLOCK) and brain muscle ARNT-like1 (BMAL1), the major components in the regulation of circadian rhythm, has been identified in the brain, the mechanism by which CLOCK and BMAL1 regulates the dysfunction of astrocytes in AD remains unclear. Here, we show that the protein levels of CLOCK and BMAL1 are significantly elevated in impaired astrocytes of cerebral cortex from patients with AD. We demonstrate that the over-expression of CLOCK and BMAL1 significantly suppresses aerobic glycolysis and lactate production by the reduction in hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) protein levels in human astrocytes. Moreover, the elevation of CLOCK and BMAL1 induces functional impairment by the suppression of glial fibrillary acidic protein (GFAP)-positive filaments in human astrocytes. Furthermore, the elevation of CLOCK and BMAL1 promotes cytotoxicity by the activation of caspase-3-dependent apoptosis in human astrocytes. These results suggest that the elevation of CLOCK and BMAL1 contributes to the impairment of astrocytes by inhibition of aerobic glycolysis in AD.

show abstract

NMR metabolomic investigation of astrocytes interacted with Aβ42 or its complexes with either copper(II) or zinc(II)

Cited by 15 publications

References 85 publications

Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against Metal-Associated Amyloid β-Protein Aggregation and Cytotoxicity

Iminodiacetic Acid-Modified Human Serum Albumin: A Multifunctional Agent against Metal-Associated Amyloid β-Protein Aggregation and Cytotoxicity

Metal complexes of amino acids and peptides

Elevated CLOCK and BMAL1 Contribute to the Impairment of Aerobic Glycolysis from Astrocytes in Alzheimer’s Disease

Contact Info

Product

Resources

About