Article
Biochemistry & Molecular Biology
Ratnakar Jadhav, Yogesh A. Kulkarni
Summary: Alzheimer's disease is a neurodegenerative condition characterized by progressive loss of memory and cognitive dysfunction, particularly in older individuals. The prevalence of the disease has increased due to the global aging population. Current treatments for Alzheimer's disease have limited efficacy and adverse effects. Recent research suggests that natural products, such as baicalein, could be potential treatment options for Alzheimer's disease. Baicalein, a flavonoid from the flavone subclass, has shown neuroprotective properties through its antioxidant, anti-inflammatory, AChE enzyme inhibitory, and anti-amyloid protein aggregation activities.
Article
Biochemistry & Molecular Biology
Cong Duc Nguyen, Gihyun Lee
Summary: Melittin, the main component of honeybee venom, has been found to exhibit neuroprotective actions by alleviating oxidative stress and memory impairment in both in vitro and in vivo models. It effectively protects neuronal cells by regulating reactive oxygen species and apoptosis-related factors, while enhancing antioxidant defense pathways. Melittin also activates neurogenesis pathways and improves cognitive deficits, suggesting its potential as a therapeutic agent for neurodegenerative disorders.
Article
Biochemistry & Molecular Biology
Silvia De Caro, Giulia De Soricellis, Simone Dell'Acqua, Enrico Monzani, Stefania Nicolis
Summary: Both beta-amyloid peptides and oxidative stress are important factors in Alzheimer's disease. Hemin, which has redox properties, contributes to the disease's development and its level increases in pathological conditions and traumatic brain injuries. This study aimed to investigate the reactivity of the hemin-beta-amyloid(16) complex and found that it can catalyze oxidation and nitration reactions. The results showed that the complex binds negatively charged substrates with higher affinity and the tyrosine residue is the target of nitration. The study also found that hemin degradation is partly prevented by the coordinated peptide.
Article
Pharmacology & Pharmacy
Ratnakar Jadhav, Yogesh A. A. Kulkarni
Summary: Alzheimer's disease is a common form of dementia, and there are few approved medications for its treatment. Baicalein, a flavonoid, has shown neuroprotective effects, while memantine is an important drug for Alzheimer's treatment. This study investigated the combination of baicalein and memantine in treating aluminum chloride-induced neurotoxicity in rats. The combination treatment showed significant improvement in behavior, reduced oxidative stress and amyloid plaque formation, and increased BDNF expression. These findings suggest that baicalein and memantine may slow neurodegeneration progression.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chiara Bacchella, Simone Dell'Acqua, Stefania Nicolis, Enrico Monzani, Luigi Casella
Summary: The redox chemistry of copper(II) is significantly influenced by its coordination with amyloid-beta peptides and the stability of resulting complexes. The study investigates the oxidase activity of Cu-Aβ complexes towards dopamine and catechols, revealing that Cu-II-ATCUN site is not redox-inert and catechol coordination induces metal reduction. Additionally, vicinal histidines provide a secondary Cu-binding motif independently of the ATCUN site, affecting the oxidative reactivity towards catechol.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Ahmed Mohsen Elsaid Hamdan, Fatimah Hussain J. Alharthi, Ahmed Hadi Alanazi, Soad Z. El-Emam, Sameh S. Zaghlool, Kamel Metwally, Sana Abdulaziz Albalawi, Yahia S. Abdu, Reda El-Sayed Mansour, Hoda A. Salem, Zakaria Y. Abd Elmageed, Karema Abu-Elfotuh
Summary: The study demonstrates that phytochemicals combined with physical and mental activities have neuroprotective effects on an aluminum-induced Alzheimer's disease rat model, slowing down the progression of the disease by modulating multiple signaling pathways.
Review
Biochemistry & Molecular Biology
Elena Tamagno, Michela Guglielmotto, Valeria Vasciaveo, Massimo Tabaton
Summary: The pathogenesis of Alzheimer's disease involves the accumulation of beta amyloid and vulnerability of the brain to oxidative stress, which are linked to each other. It is difficult to determine which comes first, Aβ or oxidative stress. Evidence suggests that oxidative stress occurs early in the development of Alzheimer's disease and plays a crucial role in the manifestation of clinical and pathological symptoms.
Article
Biochemistry & Molecular Biology
Barbara B. Martins, Natalia G. Hosch, Queren A. Alcantara, Grant R. Budas, Che-Hong Chen, Daria Mochly-Rosen, Julio C. B. Ferreira, Vanessa O. Zambelli
Summary: The activation of the PKC epsilon-ALDH2 axis plays a crucial role in mitigating aldehyde-mediated pain in rodents, with potential implications for pain management in patients. Selective activation of this axis could provide a novel treatment approach for pain relief.
Article
Immunology
Bushra Shal, Adnan Khan, Ashraf Ullah Khan, Rahim Ullah, Muhammad Naveed, Gowhar Ali, Salman Ul Islam, Ihsan ul Haq, Bushra Mirza, Salman Khan
Summary: The present study investigated the therapeutic effects of Coagulansin-A (Coag-A) against Alzheimer's disease (AD) by inhibiting amyloid beta (Aβ) aggregation and reducing oxidative stress. Coag-A showed neuroprotective effects and attenuated cognitive decline in a mouse model of AD. It also exhibited anti-inflammatory, antioxidant, and anti-apoptotic effects by regulating the expression of nuclear factor erythroid-2-related factor (Nrf-2) and nuclear factor kappa B (NF-κB).
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chenju Yi, Ket Yin Goh, Lik-Wei Wong, Ajeena Ramanujan, Kazuhiro Tanaka, Sreedharan Sajikumar, Carlos F. Ibanez
Summary: In this study, it was found that mice expressing signaling-deficient variants of the p75 neurotrophin receptor showed greater neuroprotection from AD neuropathology in an animal model of AD. These variants interact with amyloid precursor protein (APP) at the plasma membrane and regulate its internalization, affecting amyloidogenic processing and disease progression. This suggests that inhibitors targeting the p75(NTR) transmembrane domain may be an effective therapeutic strategy in AD.
Article
Chemistry, Analytical
Yu P. Zhang, Evgeniia Lobanova, Derya Emin, Sergey V. Lobanov, Antonina Kouli, Caroline H. Williams-Gray, David Klenerman
Summary: This study introduces a new method for the diagnosis of early Parkinson's disease. The results show that the proportion of soluble alpha-synuclein aggregates can distinguish between Parkinson's disease patients and control groups, with Parkinson's disease patients having a higher proportion of larger and rounder alpha-synuclein aggregates. By combining the number and morphology of the aggregates, a new biomarker with improved accuracy for early Parkinson's disease diagnosis was constructed.
ANALYTICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Lucia Gallego Villarejo, Lisa Bachmann, David Marks, Maite Brachthaeuser, Alexander Geidies, Thorsten Mueller
Summary: Intracellular amyloid beta (iAβ) plays a crucial role in neurodegeneration and serves as a pathological marker. Modulating iAβ through pharmacological treatment has shown beneficial effects on cognitive properties. Future research should focus on the impact of viral infections on iAβ generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Rehana Khatoon, Pooja Kaushik, Suhel Parvez
Summary: Alzheimer's disease is a complex neurological disorder with limited treatment options, while minocycline has been shown to potentially have a therapeutic effect against AD. Research on the molecular mechanisms involved in AD pathogenesis using minocycline treated transgenic AD flies could provide valuable insights.
Article
Chemistry, Medicinal
Jun Liu, Ying Meng, Ming-Han Yang, Xiao-Yi Zhang, Jian-Fu Zhao, Ping-Hua Sun, Wei-Min Chen
Summary: In this study, several 3-hydroxypyridin-4(1H)-one hybrids were designed and synthesized, and their potential as inhibitors of P. aeruginosa biofilm formation was evaluated. The most active compound, 12h, exhibited significant biofilm inhibitory activity. Mechanistic studies revealed that 12h inhibited biofilm formation by suppressing the expression of lasB and pqsA. Furthermore, 12h improved the antibiotic susceptibility of P. aeruginosa and reduced its acute virulence in Vero cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ceyhan Hacioglu, Fatih Kar, Ezgi Kar, Yakup Kara, Gungor Kanbak
Summary: Synaptosomes serve as a valuable ex vivo model for studying neuronal transmission and neurodegenerative processes. The study found that boric acid and curcumin have protective effects on rat brain synaptosomes against A beta 1-42 induced damage. Boric acid and curcumin treatment can prevent alterations in the cholinergic system and inhibit oxidative stress in synapses of the cerebral cortex exposed to A beta 1-42.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2021)
Editorial Material
Neurosciences
Luigi Zecca, Christian Pifl, Stanley Fahn, David Sulzer, Ruggero G. Fariello
Summary: By studying Parkinson's disease and the treatment with L-DOPA, Hornykiewicz improved the lives of many individuals and made significant contributions to neurology and medical science.
NPJ PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Kirsty E. McAleese, Sean J. Colloby, Alan J. Thomas, Safa Al-Sarraj, Olaf Ansorge, James Neal, Federico Roncaroli, Seth Love, Paul T. Francis, Johannes Attems
Summary: The aged brain often exhibits multiple pathologies, rather than a single pathology, and the presence of multiple pathologies can significantly worsen cognitive decline, increasing the risk of transitioning from mild cognitive impairment to dementia.
ALZHEIMERS & DEMENTIA
(2021)
Article
Clinical Neurology
Clara Y. B. Low, Jasinda H. Lee, Frances T. W. Lim, Chingli Lee, Clive Ballard, Paul T. Francis, Mitchell K. P. Lai, Michelle G. K. Tan
Summary: Studies have shown selective upregulation of FynT expression in the neocortex of patients with Alzheimer's disease, Parkinson's disease dementia, and dementia with Lewy bodies, which correlated with cognitive impairment, neuropathological lesions, soluble beta-amyloid, phosphorylated tau, and markers of microglia and astrocyte activation. This suggests that FynT may play a role in neurodegenerative dementias through effects on tauopathy and neuroinflammation.
Article
Neurosciences
Katriona L. Hole, Lydia E. Staniaszek, Gayathri Menon Balan, Jody M. Mason, Jon T. Brown, Robert J. Williams
Summary: Oral administration of EC reduces a specific phosphorylated form of tau in rTg4510 mice and inhibits its phosphorylation, independently of GSK3 beta regulation.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Richard M. Meade, Kathryn J. C. Watt, Robert J. Williams, Jody M. Mason
Summary: A peptide inhibitor was derived from a cell library screen to block aggregation of alpha-synuclein (α S) and its conversion into toxic species. Truncation and alanine scan analysis were used to determine inhibitory residues and improve peptide efficacy without disrupting α S lipid-binding. This work aims to develop a potent peptide antagonist of α S pathogenicity while preserving its native function.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Robert J. Williams, Kochupurackal P. Mohanakumar, Philip M. Beart
Summary: This special issue compiles contributions from experts in nutraceutical research, providing an overview of how chemically identified molecules from natural products can benefit brain function, as well as how herbal medicines can improve brain function in various models of brain injury through their multi-targeted actions.
NEUROCHEMISTRY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Kathryn J. C. Watt, Richard M. Meade, Robert J. Williams, Jody M. Mason
Summary: This study identified five peptides that have inhibitory effects on the aggregation of Parkinson's disease (PD) related protein variants. These peptides not only reduce the aggregation of PD-associated proteins, but also show the same efficacy when incubated with other variants. Additionally, the optimized peptide 4554W(N6A) is highly effective against wild-type protein and several single-point mutant forms, providing a suitable baseline for further PD therapeutic research.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Neurosciences
Eduardo Molina-Holgado, Pedro F. Esteban, Angel Arevalo-Martin, Rafael Moreno-Luna, Francisco Molina-Holgado, Daniel Garcia-Ovejero
Summary: Oligodendrocytes in the central nervous system synthesize myelin and have the ability to regulate their functions through interactions with other cells and sensing the environment. They respond to various signals, including the endocannabinoid signaling, which has therapeutic potential for promoting remyelination in central nervous system pathologies.
Article
Biochemistry & Molecular Biology
Gareth Williams, David Chambers, Ruman Rahman, Francisco Molina-Holgado
Summary: By performing a transcriptional analysis of AM630 activity in different cell lines of glioblastoma, we found significant differences in gene expression profiles between core cells and invasive margin cells. Only the core cells expressed the potential target of AM630, the CB1 receptor, while the HTR2B serotonin receptor was moderately expressed in both cell types. Additionally, the AM630-driven transcriptional response was stronger in core cells, resulting in upregulation of immune response and downregulation of cell cycle and metastatic pathways.
Article
Multidisciplinary Sciences
Cigdem Gelegen, Diana Cash, Katarina Ilic, Millie Sander, Eugene Kim, Camilla Simmons, Michel Bernanos, Joana Lama, Karen Randall, Jonathan T. Brown, Svjetlana Kalanj-Bognar, Samuel Cooke, K. Ray Chaudhuri, Clive Ballard, Paul Francis, Ivana Rosenzweig
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Ioanna Pavlaki, Michael Shapiro, Giuseppina J. Pisignano, Stephanie M. E. R. Jones, Jelena W. Telenius, Silvia M. Munoz-Descalzo, Robert Williams, Jim M. Hughes, Keith Vance
Summary: Central nervous system-expressed long non-coding RNAs (lncRNAs) are often located near protein coding genes involved in transcriptional control. The study identified the cis-regulatory interactions controlling the co-expression of the Paupar-Pax6 lncRNA-mRNA locus in the brain. The TCF7L2 transcription factor binds to specific cis-regulatory elements to regulate the expression of Paupar and Pax6 together.
Article
Biochemistry & Molecular Biology
Jody M. Mason, Kathryn J. C. Watt, Richard M. Meade, Robert J. Williams
Summary: This article investigates the role of alpha-synuclein in synucleinopathies and explores the interplay between mutant alpha-synuclein and lipids.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Gemma Shireby, Emma L. Dempster, Stefania Policicchio, Rebecca G. Smith, Ehsan Pishva, Barry Chioza, Jonathan P. Davies, Joe Burrage, Katie Lunnon, Dorothea Seiler Vellame, Seth Love, Alan Thomas, Keeley Brookes, Kevin Morgan, Paul Francis, Eilis Hannon, Jonathan Mill
Summary: This study identified differences in cortical DNA methylation associated with Alzheimer's disease pathology and found that most of these differences occurred in non-neuronal cells.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Zunera Khan, Miguel Vasconcelos Da Silva, Kayleigh-Marie Nunez, Chris Kalafatis, Steven Nowicki, Zuzana Walker, Ingelin Testad, Paul Francis, Clive Ballard
Summary: The study found that impairment of non-verbal communication among nursing home residents with dementia was independently associated with the severity of neuropsychiatric symptoms (NPS) and quality of life (QoL). This highlights a novel potential approach to improve NPS and QoL using elements of non-verbal communication, particularly for individuals with severe dementia.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2021)
Article
Medicine, General & Internal
Sube Banerjee, Juliet High, Susan Stirling, Lee Shepstone, Ann Marie Swart, Tanya Telling, Catherine Henderson, Clive Ballard, Peter Bentham, Alistair Burns, Nicolas Farina, Chris Fox, Paul Francis, Robert Howard, Martin Knapp, Iracema Leroi, Gill Livingston, Ramin Nilforooshan, Shirley Nurock, John O'Brien, Annabel Price, Alan J. Thomas, Naji Tabet
Summary: This study evaluated the efficacy and safety of mirtazapine, an antidepressant, for treating agitation in patients with dementia. The findings showed that mirtazapine did not reduce agitation symptoms compared to placebo, and there was a potentially higher mortality rate associated with mirtazapine use.
