A Comparative Interaction between Copper Ions with Alzheimer's<i>β</i>Amyloid Peptide and Human Serum Albumin

Behbehani, G. Rezaei; Barzegar, L.; Mohebbian, M.; Saboury, Ali Akbar

doi:10.1155/2012/208641

Cited by 10 publications

(11 citation statements)

References 19 publications

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“…In vitro , removal of Cu 2+ from Aβ prevents its accumulation [ 243 , 244 , 245 ], leads to its degradation, stops hydroxyl radical (•OH) production and oxidative damage, and finally reduces cell death [ 245 ]. For the effects as mentioned above, researches have suggested potential metal chelation therapy for AD [ 246 , 247 , 248 , 249 , 250 , 251 , 252 ].…”

Section: Therapeutics To Tackle Copper Ions In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

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Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.

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Section: Therapeutics To Tackle Copper Ions In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

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“…Elimination of Cu 2+ from β-amyloid prevents amyloid aggregation in vitro ( Wu et al, 2008 ; Behbehani et al, 2012 ), and promotes β-amyloid degradation, and prevents H 2 O 2 formation. Hence, it also decreases cell mortality ( Wu et al, 2008 ).…”

Section: Copper Ion Toxicity In Admentioning

confidence: 99%

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

Bagheri

Squitti

Haertlé

et al. 2018

Front. Aging Neurosci.

183

121

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Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by amyloid plaques in patients’ brain tissue. The plaques are mainly made of β-amyloid peptides and trace elements including Zn2+, Cu2+, and Fe2+. Some studies have shown that AD can be considered a type of metal dyshomeostasis. Among metal ions involved in plaques, numerous studies have focused on copper ions, which seem to be one of the main cationic elements in plaque formation. The involvement of copper in AD is controversial, as some studies show a copper deficiency in AD, and consequently a need to enhance copper levels, while other data point to copper overload and therefore a need to reduce copper levels. In this paper, the role of copper ions in AD and some contradictory reports are reviewed and discussed.

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“…Upon interaction, HSA’s inhibitory effects have been reported toward the aggregations of several amyloid proteins such as IDPs like Aβ, α-synuclein, and tau proteins . Owing to the potential of HSA as an amyloid aggregation inhibitor, ,− we have examined here the effect of HSA on the aggregation of a C-terminal fragment of TDP-43 protein, TDP-43 2C , which also harbors an intrinsically disordered C-terminal domain. We investigated in vitro the effect of different concentrations of HSA on the TDP-43 2C aggregation in the view that both proteins can be present in the CSF.…”

Section: Discussionmentioning

confidence: 99%

“…34−36 HSA is known to be a potential amyloid aggregation inhibitor, as it directly binds to the IDPs or their toxic oligomers, 37 which include Aβ species, 38 α-Synuclein, 39−41 insulin, 29 and islet amyloid polypeptide, 42 and it is also an antioxidant that chelates toxic redox metal ions. 43,44 In view of the observed elevated serum and CSF levels of TDP-43 protein in ALS patients and HSA being an abundant protein in the serum and CSF, here we examined in vitro if HSA can affect the aggregation of TDP-43 C-terminal fragment (aa: 193−414), TDP-43 2C . We first performed an in vitro thioflavin T (ThT) fluorescence kinetics assay to determine the TDP-43 2C aggregation pattern alone or in the presence of HSA at different stoichiometric ratios.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Notably, HSA produced by ultrafiltration of plasma proteins and by the microglia results in its presence as the most abundant protein (approximately 80%) among the CSF and enters across the blood-brain barrier by molecular diffusion . Furthermore, for amyloidogenic disorder one of the viable therapeutic approaches is to identify the amyloid inhibitor that disrupts the intrinsically disordered proteins (IDPs) association. − HSA is known to be a potential amyloid aggregation inhibitor, as it directly binds to the IDPs or their toxic oligomers, which include Aβ species, α-Synuclein, − insulin, and islet amyloid polypeptide, and it is also an antioxidant that chelates toxic redox metal ions. , …”

Section: Introductionmentioning

confidence: 99%

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In Vitro Interaction of a C-Terminal Fragment of TDP-43 Protein with Human Serum Albumin Modulates Its Aggregation

et al. 2022

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An increased level of naturally occurring anti-TDP-43 antibodies was observed in the serum and cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis patients. Human serum albumin (HSA), the most abundant protein in blood plasma and CSF, is found to interact with pathological proteins like Aβ and α-synuclein. Therefore, we examined the effect on the in vitro aggregation of a C-terminal fragment of TDP-43 in the presence of HSA. We found that the lag phase in TDP-43 2C aggregation is abrogated in the presence of HSA, but there is an overall decreased aggregation as examined by thioflavin-T fluorescence spectroscopy and microscopy. An early onset of TDP-43 2C oligomer formation in the presence of HSA was observed using atomic force microscopy and transmission electron microscopy. Also, a known chemical inhibitor of TDP-43 2C aggregation, AIM4, abolishes the HSA-induced early formation of TDP-43 2C oligomers. Notably, the aggregates of TDP-43 2C formed in the presence of HSA are more stable against sarkosyl detergent. Using affinity copurification, we observed that HSA can bind to TDP-43 2C , and biolayer interferometry further supported their physical interaction and suggested the binding affinity to be in sub-micromolar range. Taken together, the data support that HSA can interact with TDP-43 2C in vitro and affect its aggregation.

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A Comparative Interaction between Copper Ions with Alzheimer'sβAmyloid Peptide and Human Serum Albumin

Cited by 10 publications

References 19 publications

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

In Vitro Interaction of a C-Terminal Fragment of TDP-43 Protein with Human Serum Albumin Modulates Its Aggregation

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