Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease

Šalković‐Petrišić, Melita; Knezović, Ana; Osmanovic-Barilar, Jelena; Smailović, Una; Trkulja, Vladimir; Riederer, Peter; Amit, Tamar; Mandel, Silvia; Youdim, Moussa B. H.

doi:10.1016/j.lfs.2015.06.026

Cited by 41 publications

(40 citation statements)

References 60 publications

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“…Further experiments showed that the multifunctional iron chelator HLA20 also exerted neuroprotective effects in STZ (i.c.v. )‐induced memory impairments (Šalković‐Petrišić et al ., ) (Table ).…”

Section: Iron‐chelating and Mao Inhibitory Compoundsmentioning

confidence: 99%

Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β‐amyloid in ageing and Alzheimer's disease

Weinreb

Amit

Bar-Am

et al. 2015

British J Pharmacology

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Alzheimer's disease (AD) is accepted nowadays as a complex neurodegenerative disorder with multifaceted cerebral pathologies, including extracellular deposition of amyloid β peptide-containing plaques, intracellular neurofibrillary tangles, progressive loss of cholinergic neurons, metal dyshomeostasis, mitochondrial dysfunction, neuroinflammation, glutamate excitoxicity, oxidative stress and increased MAO enzyme activity. This may explain why it is currently widely accepted that a more effective therapy for AD would result from the use of multifunctional drugs, which may affect more than one brain target involved in the disease pathology. The current review will discuss the potential benefits of novel multimodal neuroprotective, brain permeable drugs, recently developed by Youdim and collaborators, as a valuable therapeutic approach for AD treatment. The pharmacological and neuroprotective properties of these multitarget-directed ligands, which target MAO enzymes, the cholinergic system, iron accumulation and amyloid β peptide generation/aggregation are described, with a special emphasis on their potential therapeutic value for ageing and AD-associated cognitive functions. This review is conceived as a tribute to the broad neuropharmacology work of Professor Moussa Youdim, Professor Emeritus in the

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Section: Iron‐chelating and Mao Inhibitory Compoundsmentioning

confidence: 99%

Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β‐amyloid in ageing and Alzheimer's disease

Weinreb

Amit

Bar-Am

et al. 2015

British J Pharmacology

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“…Streptozotocin (STZ) treatment. The rats were subjected to general anaesthesia (ket amine 50 mg/kg/xylazine 5 mg/kg ip) and given STZ bilaterally into each lateral ventricle (2 µL/ventricle) in a total dose of 3 mg/kg (dissolved in 0.05 M citrate buffer, pH 4.5, split in two doses on day 1 and 3), according to the procedure first described by Noble et al [50] and used afterwards in our experiments [5,15,32,51]. the required concentration was adjusted to the rat body weight, measured on a weekly basis).…”

Section: Drug Treatmentsmentioning

confidence: 99%

Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

et al. 2018

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“…Although the explanation for this imbalance is still unknown, studies on the role of iron in AD have shown that excessive iron stimulates hydroxyl radical formation via the Fenton reaction, which may contribute to increased oxidative stress levels in AD. Oxidative damage to AD-linked protein aggregations by excessive levels of iron can cause synaptic dysfunction and neuronal cell death, a detrimental process which can be alleviated by the administration of iron chelators ( Salkovic-Petrisic et al, 2015 ). High iron content is loaded around senile plaques and elevates the production of Aβ by increasing the expression of amyloid-β precursor protein (APP).…”

Section: Biometals and Their Transportersmentioning

confidence: 99%

Biometal Dyshomeostasis and Toxic Metal Accumulations in the Development of Alzheimer’s Disease

Jiao

et al. 2017

Front. Mol. Neurosci.

104

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Biometal dyshomeostasis and toxic metal accumulation are common features in many neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease, and Huntington’s disease. The neurotoxic effects of metal imbalance are generally associated with reduced enzymatic activities, elevated protein aggregation and oxidative stress in the central nervous system, in which a cascade of events lead to cell death and neurodegeneration. Although the links between biometal imbalance and neurodegenerative disorders remain elusive, a major class of endogenous proteins involved in metal transport has been receiving increasing attention over recent decades. The abnormal expression of these proteins has been linked to biometal imbalance and to the pathogenesis of AD. Here, we present a brief overview of the physiological roles of biometals including iron, zinc, copper, manganese, magnesium and calcium, and provide a detailed description of their transporters and their synergistic involvement in the development of AD. In addition, we also review the published data relating to neurotoxic metals in AD, including aluminum, lead, cadmium, and mercury.

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Multi-target iron-chelators improve memory loss in a rat model of sporadic Alzheimer's disease

Cited by 41 publications

References 60 publications

Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β‐amyloid in ageing and Alzheimer's disease

Neuroprotective effects of multifaceted hybrid agents targeting MAO, cholinesterase, iron and β‐amyloid in ageing and Alzheimer's disease

Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Biometal Dyshomeostasis and Toxic Metal Accumulations in the Development of Alzheimer’s Disease

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