Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease

González, Paulina; Costa, Viviana C. P. da; Hyde, Kimberly; Wu, Qiong; Annunziata, Onofrio; Rizo, Josep; Akkaraju, Giridhar R.; Green, Kayla N.

doi:10.1039/c4mt00161c

Cited by 26 publications

(37 citation statements)

References 44 publications

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“…Alzheimer's disease (AD) is the most common neurodegenerative disorder that causes dementia and affects middle to old-aged individuals (Hager et al, 2001 ; Gonzalez et al, 2014 ; Irwin et al, 2016 ). AD is characterized by progressive loss of cognitive functions, including memory, language, and reasoning (Di Domenico et al, 2015 ).…”

Section: Effects Of La In Experimental Models Of Memory Deficits Assomentioning

confidence: 99%

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

Molz

Schröder

2017

Front. Pharmacol.

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The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure. Lipoic acid (LA), a natural compound present in food and used as a dietary supplement, has been considered a promising agent for the treatment and/or prevention of neurodegenerative disorders. In spite of a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect, to date only a few studies have examined its effects in humans. Investigations performed in animal models of memory loss associated to aging and neurodegenerative disorders have shown that LA improves memory in a variety of behavioral paradigms. Moreover, cell and molecular mechanisms underlying LA effects have also been investigated. Accordingly, LA displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions. The present review article aimed at summarizing and discussing the main studies investigating the effects of LA on cognition as well as its cell and molecular effects, in order to improve the understanding of the therapeutic potential of LA on memory loss during aging and in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with LA.

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Section: Effects Of La In Experimental Models Of Memory Deficits Assomentioning

confidence: 99%

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

Molz

Schröder

2017

Front. Pharmacol.

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“…Thus, determining structural backbones or moieties important for notable reactivity with metal‐free Aβ and metal–Aβ from naturally occurring flavonoids would provide insight into developing chemical reagents that are useful for elucidating Aβ‐related pathology in AD at the molecular level. Moreover, the structural variations of flavonoids with biocompatible functional groups may further enhance their applicability as diagnostics and therapeutics for AD 72,73 …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the structural variations of flavonoids with biocompatible functional groups may further enhance their applicability as diagnostics and therapeutics for AD. 72,73…”

Section: Discussionmentioning

confidence: 99%

Reactivity of Flavonoids Containing a Catechol or Pyrogallol Moiety with Metal‐Free and Metal‐Associated Amyloid‐β

Park

Lim

2020

Bulletin Korean Chem Soc

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Aggregates of both metal-free amyloid-β (Aβ) and metal-bound Aβ (metal-Aβ) are accumulated in the brain affected by Alzheimer's disease. To control metal-free and metal-bound Aβ species, chemical reagents capable of modulating their aggregation profiles have been developed. As an effort, the reactivity of natural products such as flavonoids with metal-free Aβ and metal-Aβ has been investigated to identify their use as chemical reagents and structural features essential for such reactivity. This review illustrates the effects of flavonoids containing a catechol or pyrogallol group on metal-free and metal-mediated Aβ aggregation pathways. In addition, the studies regarding the structure-activity relationship of flavonoids against metal-free Aβ or metal-Aβ are discussed.

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“…The generation and release of ACh is lessened and the numbers of presynaptic cholinergic receptors are diminished. In Aβ42induced AD, choline acetyltransferase in synaptosomes experiences oxidative modification and enzymatic activities are decreased (22). The pathogenesis of AD involves numerous factors and oxidative stress may be the trigger for a series of complex events.…”

Section: Discussionmentioning

confidence: 99%

Effects of caffeic acid on learning deficits in a model of Alzheimer's disease

Wang

et al. 2016

International Journal of Molecular Medicine

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Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factor‑κB‑p65 protein expression and caspase‑3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway.

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Bimodal-hybrid heterocyclic amine targeting oxidative pathways and copper mis-regulation in Alzheimer's disease

Cited by 26 publications

References 44 publications

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

Reactivity of Flavonoids Containing a Catechol or Pyrogallol Moiety with Metal‐Free and Metal‐Associated Amyloid‐β

Effects of caffeic acid on learning deficits in a model of Alzheimer's disease

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