Bioinorganic Chemistry of Alzheimer’s Disease

Chemical Reviews, Journal Year: 2012, Volume and Issue: 112(10), P. 5193 - 5239

Published: July 13, 2012

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTBioinorganic Chemistry of Alzheimer's DiseaseKasper P. Kepp*View Author Information DTU Chemistry, Technical University Denmark, DK 2800 Kongens Lyngby, Denmark*E-mail: [email protected]Cite this: Chem. Rev. 2012, 112, 10, 5193–5239Publication Date (Web):July 13, 2012Publication History Received12 January 2012Published online13 July inissue 10 October 2012https://pubs.acs.org/doi/10.1021/cr300009xhttps://doi.org/10.1021/cr300009xreview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views14664Altmetric-Citations568LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF and HTML) across all institutions individuals. These metrics regularly updated to reflect usage leading up last few days.Citations number other articles citing this article, calculated by Crossref daily. Find more information about citation counts.The Altmetric Attention Score is a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence for given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Ions,Metals,Oxidative stress,Peptides proteins,Zinc Get e-Alerts

Language: Английский

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History and progress of hypotheses and clinical trials for Alzheimer’s disease

Signal Transduction and Targeted Therapy, Journal Year: 2019, Volume and Issue: 4(1)

Published: Aug. 23, 2019

Abstract Alzheimer’s disease (AD) is a neurodegenerative characterized by progressive memory loss along with neuropsychiatric symptoms and decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, neurofibrillary tangles the brains patients. There various descriptive hypotheses regarding causes AD, including cholinergic hypothesis, tau propagation mitochondrial cascade calcium homeostasis neurovascular inflammatory metal ion lymphatic system hypothesis. However, ultimate etiology AD remains obscure. In this review, we discuss related clinical trials. Wealthy puzzles lessons have made it possible to develop explanatory theories identify potential strategies for therapeutic interventions AD. The combination hypometabolism autophagy deficiency likely be causative factor We further propose that fluoxetine, selective serotonin reuptake inhibitor, has treat

Language: Английский

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Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(2), P. 1221 - 1322

Published: Aug. 10, 2018

Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow negative outlook. Although large amount research has been dedicated to elucidating pathologies neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, neurotransmitter deficiencies are pathological features shared across multiple disorders. In addition, these factors proposed be interrelated upon disease progression. Thus, development multifunctional compounds capable simultaneously interacting with several components suggested as solution undertake complex diseases. this review, we outline discuss possible therapeutic targets in Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis molecules, previously designed or discovered potential drug candidates for disorders emphasis multifunctionality. underrepresented areas discussed indicate new directions.

Language: Английский

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Biological metals and metal-targeting compounds in major neurodegenerative diseases

Chemical Society Reviews, Journal Year: 2014, Volume and Issue: 43(19), P. 6727 - 6749

Published: Jan. 1, 2014

Metals are functionally essential, but redistribute in neurodegenerative disease where they induce protein aggregates, catalyze radical formation, and lose bioavailability.

Language: Английский

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Copper, zinc and iron in neurodegenerative diseases (Alzheimer's, Parkinson's and prion diseases)

Coordination Chemistry Reviews, Journal Year: 2012, Volume and Issue: 256(19-20), P. 2129 - 2141

Published: March 30, 2012

Language: Английский

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Untangling Amyloid-β, Tau, and Metals in Alzheimer’s Disease

ACS Chemical Biology, Journal Year: 2013, Volume and Issue: 8(5), P. 856 - 865

Published: March 18, 2013

Protein misfolding and metal ion dyshomeostasis are believed to underlie numerous neurodegenerative diseases, including Alzheimer's disease (AD). The pathological hallmark of AD is accumulation misfolded amyloid-β (Aβ) peptides hyperphosphorylated tau (ptau) proteins in the brain. Since etiology remains unclear, several hypotheses have emerged elucidate its pathways. amyloid cascade hypothesis, a leading hypothesis for development, advocates Aβ as principal culprit. Additionally, evidence suggests that may contribute pathology. also been shown impact each other's pathology either directly or indirectly. Furthermore, associated with these proteins. Metal interactions tau/ptau influence their aggregation properties neurotoxicity. Herein, we present current understanding on roles Aβ, tau, ions, placing equal emphasis proposed features, well inter-relationships pathogenesis.

Language: Английский

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Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer’s Disease

Journal of the American Chemical Society, Journal Year: 2013, Volume and Issue: 135(44), P. 16397 - 16409

Published: Oct. 11, 2013

In this article, we first designed and synthesized curcumin-based near-infrared (NIR) fluorescence imaging probes for detecting both soluble insoluble amyloid beta (Aβ) species then an inhibitor that could attenuate cross-linking of Aβ induced by copper. According to our previous results the possible structural stereohindrance compatibility peptide hydrophobic/hydrophilic property Aβ13-20 (HHQKLVFF) fragment, NIR probe CRANAD-58 was synthesized. As expected showed significant changes upon mixing with in vitro. vivo revealed capable differentiating transgenic wild-type mice as young 4 months old, age lacks apparently visible plaques is likely its forms. limited studies on interaction mechanism between Aβ, also CRANAD-17 Aβ42 It well-known coordination copper imidazoles Histidine-13 14 (H13, H14) peptides initialize covalent Aβ. CRANAD-17, a curcumin scaffold used anchoring moiety usher compound vicinity H13 H14 imidazole rings were incorporated compete H13/H14 binding. The SDS-PAGE gel Western blot indicated inhibiting This raises potential be considered AD therapy.

Language: Английский

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Role of metal dyshomeostasis in Alzheimer's disease

Metallomics, Journal Year: 2011, Volume and Issue: 3(3), P. 267 - 267

Published: Jan. 1, 2011

Despite serving a crucial purpose in neurobiological function, transition metals play sinister part the aging brain, where abnormal accumulation and distribution of reactive iron, copper, zinc elicit oxidative stress macromolecular damage that impedes cellular function. Alzheimer's disease (AD), an age-related neurodegenerative condition, presents marked accumulations stress-induced damage, increasing evidence points to aberrant metal homeostasis as critical factor its pathogenesis. Amyloid-β oligomerization fibrillation, considered by many be precipitating underlying AD onset development, is also induced activity. We here elaborate on roles describe therapeutic implications they present.

Language: Английский

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Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols

Coordination Chemistry Reviews, Journal Year: 2012, Volume and Issue: 256(19-20), P. 2333 - 2356

Published: March 17, 2012

Language: Английский

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Neuropathology and biochemistry of Aβ and its aggregates in Alzheimer’s disease

Acta Neuropathologica, Journal Year: 2014, Volume and Issue: 129(2), P. 167 - 182

Published: Dec. 22, 2014

Language: Английский

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