scholarly journals Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6531
Author(s):  
María Jesús Friedli ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Molecular Mechanisms ◽  
Acetylcholinesterase Inhibitor ◽  
Amyloid Β ◽  
Huperzine A ◽  
Amyloid Β Peptide ◽  
Molecular Signaling ◽  
Neuroprotective Effects ◽  
App Processing

Huperzine A (HupA), an alkaloid found in the club moss Huperzia serrata, has been used for centuries in Chinese folk medicine to treat dementia. The effects of this alkaloid have been attributed to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), acting as an acetylcholinesterase inhibitor (AChEI). The biological functions of HupA have been studied both in vitro and in vivo, and its role in neuroprotection appears to be a good therapeutic candidate for Alzheimer´s disease (AD). Here, we summarize the neuroprotective effects of HupA on AD, with an emphasis on its interactions with different molecular signaling avenues, such as the Wnt signaling, the pre- and post-synaptic region mechanisms (synaptotagmin, neuroligins), the amyloid precursor protein (APP) processing, the amyloid-β peptide (Aβ) accumulation, and mitochondrial protection. Our goal is to provide an integrated overview of the molecular mechanisms through which HupA affects AD.

scholarly journals Neuropharmacological Effects of Quercetin: A Literature-Based Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Md. Shahazul Islam ◽  
Cristina Quispe ◽  
Rajib Hossain ◽  
Muhammad Torequl Islam ◽  
Ahmed Al-Harrasi ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neuroprotective Effect ◽  
Animal Experiments ◽  
Amyloid Β ◽  
Neuronal Injury ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Neuroprotective Effects

Quercetin (QUR) is a natural bioactive flavonoid that has been lately very studied for its beneficial properties in many pathologies. Its neuroprotective effects have been demonstrated in many in vitro studies, as well as in vivo animal experiments and human trials. QUR protects the organism against neurotoxic chemicals and also can prevent the evolution and development of neuronal injury and neurodegeneration. The present work aimed to summarize the literature about the neuroprotective effect of QUR using known database sources. Besides, this review focuses on the assessment of the potential utilization of QUR as a complementary or alternative medicine for preventing and treating neurodegenerative diseases. An up-to-date search was conducted in PubMed, Science Direct and Google Scholar for published work dealing with the neuroprotective effects of QUR against neurotoxic chemicals or in neuronal injury, and in the treatment of neurodegenerative diseases. Findings suggest that QUR possess neuropharmacological protective effects in neurodegenerative brain disorders such as Alzheimer’s disease, Amyloid β peptide, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. In summary, this review emphasizes the neuroprotective effects of QUR and its advantages in being used in complementary medicine for the prevention and treatment o of different neurodegenerative diseases.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

Neuroprotective Effects of the FGF21 Analogue LY2405319

2021 ◽  
pp. 1-13
Author(s):  
Claire Rühlmann ◽  
David Dannehl ◽  
Marcus Brodtrück ◽  
Andrew C. Adams ◽  
Jan Stenzel ◽  
...  
Keyword(s):  
Glial Cells ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Fibroblast Growth Factor 21 ◽  
Neuroprotective Effects ◽  
Organotypic Brain Slice ◽  
Brain Slice Cultures ◽  
Abca1 Mrna

Background: To date, there are no effective treatments for Alzheimer’s disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analogue LY2405319 (LY), which has a specificity and potency comparable to FGF21. Methods: The present study investigated the potential neuroprotective effect of LY via PPARγ/apoE/abca1 pathway which is known to degrade amyloid-β (Aβ) plaques by using primary glial cells and hippocampal organotypic brain slice cultures (OBSCs) from 30- and 50-week-old transgenic APPswe/PS1dE9 (tg) mice. By LY treatment of 52-week-old tg mice with advanced Aβ deposition, we further aimed to elaborate the effect of LY on AD pathology in vivo. Results: LY application to primary glial cells caused an upregulation of pparγ, apoE, and abca1 mRNA expression and significantly decreased number and area of Aβ plaques in OBSCs. LY treatment in tg mice increased cerebral [18F] FDG uptake and N-acetylaspartate/creatine ratio indicating enhanced neuronal activity and integrity. Although LY did not reduce the number of Aβ plaques in tg mice, the number of iba1-positive cells was significantly decreased indicating reduced microgliosis. Conclusion: These data identified LY in vitro as an activator of Aβ degrading genes leading to cerebral Aβ load amelioration in early and late AD pathology. Although Aβ plaque reduction by LY failed in vivo, LY may be used as therapeutic agent to treat AD-related neuroinflammation and impaired neuronal integrity.

scholarly journals Biophysical studies of protein misfolding and aggregation in in vivo models of Alzheimer's and Parkinson's diseases

2020 ◽  
Vol 53 ◽  
Author(s):  
Tessa Sinnige ◽  
Karen Stroobants ◽  
Christopher M. Dobson ◽  
Michele Vendruscolo
Keyword(s):  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Disease Modifying Drugs ◽  
Parkinson’S Diseases ◽  
Protein Misfolding And Aggregation

Abstract Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.

scholarly journals Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia

2021 ◽  
Vol 118 (15) ◽  
pp. e2025847118
Author(s):  
Dorit Trudler ◽  
Kristopher L. Nazor ◽  
Yvonne S. Eisele ◽  
Titas Grabauskas ◽  
Nima Dolatabadi ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Amyloid Β ◽  
Induced Pluripotent Stem Cell ◽  
Amyloid Β Peptide ◽  
Human Microglia ◽  
Pyrin Domain ◽  
Toll Like Receptor 2 ◽  
Induced Pluripotent

Parkinson’s disease is characterized by accumulation of α-synuclein (αSyn). Release of oligomeric/fibrillar αSyn from damaged neurons may potentiate neuronal death in part via microglial activation. Heretofore, it remained unknown if oligomeric/fibrillar αSyn could activate the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome in human microglia and whether anti-αSyn antibodies could prevent this effect. Here, we show that αSyn activates the NLRP3 inflammasome in human induced pluripotent stem cell (hiPSC)-derived microglia (hiMG) via dual stimulation involving Toll-like receptor 2 (TLR2) engagement and mitochondrial damage. In vitro, hiMG can be activated by mutant (A53T) αSyn secreted from hiPSC-derived A9-dopaminergic neurons. Surprisingly, αSyn–antibody complexes enhanced rather than suppressed inflammasome-mediated interleukin-1β (IL-1β) secretion, indicating these complexes are neuroinflammatory in a human context. A further increase in inflammation was observed with addition of oligomerized amyloid-β peptide (Aβ) and its cognate antibody. In vivo, engraftment of hiMG with αSyn in humanized mouse brain resulted in caspase-1 activation and neurotoxicity, which was exacerbated by αSyn antibody. These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger inflammation in human microglia.

scholarly journals Effects of Red Ginseng on Neural Injuries with Reference to the Molecular Mechanisms

J ◽  
2019 ◽  
Vol 2 (2) ◽  
pp. 116-127
Author(s):  
Pengxiang Zhu ◽  
Masahiro Sakanaka
Keyword(s):  
Molecular Mechanisms ◽  
Bioactive Molecules ◽  
Red Ginseng ◽  
Promising Candidate ◽  
Neuroprotective Effects ◽  
Chemical Structures ◽  
Brain And Spinal Cord ◽  
The Brain

Red ginseng, as an effective herbal medicine, has been traditionally and empirically used for the treatment of neuronal diseases. Many studies suggest that red ginseng and its ingredients protect the brain and spinal cord from neural injuries such as ischemia, trauma, and neurodegeneration. This review focuses on the molecular mechanisms underlying the neuroprotective effects of red ginseng and its ingredients. Ginsenoside Rb1 and other ginsenosides are regarded as the active ingredients of red ginseng; the anti-apoptotic, anti-inflammatory, and anti-oxidative actions of ginsenosides, together with a series of bioactive molecules relevant to the above actions, appear to account for the neuroprotective effects in vivo and/or in vitro. Moreover, in this review, the possibility is raised that more effective or stable neuroprotective derivatives based on the chemical structures of ginsenosides could be developed. Although further studies, including clinical trials, are necessary to confirm the pharmacological properties of red ginseng and its ingredients, red ginseng and its ingredients could be promising candidate drugs for the treatment of neural injuries.

Rutin as Neuroprotective Agent: From Bench to Bedside

2019 ◽  
Vol 26 (27) ◽  
pp. 5152-5164 ◽  
Author(s):  
Barbara Budzynska ◽  
Caterina Faggio ◽  
Marta Kruk-Slomka ◽  
Dunja Samec ◽  
Seyed Fazel Nabavi ◽  
...  
Keyword(s):  
Disease Burden ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Neuroprotective Effects ◽  
Brain Functions ◽  
High Prevalence ◽  
Biological Effectiveness ◽  
In Vivo Effects

Flavonoids are major dietary constituents of plant-based food found ubiquitously in plant kingdom where they are usually present in substantial amounts. Rutin is a flavonol-type polyphenol which consists of the flavonol quercetin and the disaccharide rutinose. Rutin has been reported to exert diverse biological effects such as antitumor and antimicrobial mainly associated to its antioxidant and anti-inflammatory activities. Mental, neurological, and behavioural disorders are an important and growing cause of morbidity. Most of these disorders combine a high prevalence, early onset, progressive clinical course, and impairment of critical brain functions making them a major contributor to the global disease burden. In the present work, the biological in vitro and in vivo effects and the potential therapeutic applications of rutin in neurodegenerative processes are reviewed, as well as their bioavailability and pharmacokinetics, which are essential for a better understanding of its biological effectiveness. Moreover, the present review also provides an overview of the molecular mechanisms through which rutin is proposed to exert its neuroprotective effects.

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