scholarly journals The biosynthetic origin of psychoactive kavalactones in kava

2018 ◽  
Author(s):  
Tomáš Pluskal ◽  
Michael P. Torrens-Spence ◽  
Timothy R. Fallon ◽  
Andrea De Abreu ◽  
Cindy H. Shi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Biosynthetic Pathway ◽  
Chalcone Synthase ◽  
De Novo ◽  
Piper Methysticum ◽  
Heterologous Production ◽  
Traditional Use ◽  
Plant Biochemistry ◽  
Tailoring Enzymes

AbstractFor millennia, humans have used plants for medicinal purposes. However, our limited understanding of plant biochemistry hinders the translation of such ancient wisdom into modern pharmaceuticals1. Kava (Piper methysticum) is a medicinal plant native to the Polynesian islands with anxiolytic and analgesic properties supported by over 3,000 years of traditional use as well as numerous recent clinical trials2–5. The main psychoactive principles of kava, kavalactones, are a unique class of polyketide natural products known to interact with central nervous system through mechanisms distinct from those of the prescription psychiatric drugs benzodiazepines and opioids6,7. Here we reportde novoelucidation of the biosynthetic pathway of kavalactones, consisting of seven specialized metabolic enzymes. Based on phylogenetic and crystallographic analyses, we highlight the emergence of two paralogous styrylpyrone synthases, both of which have neofunctionalized from an ancestral chalcone synthase to catalyze the formation of the kavalactone scaffold. Structurally diverse kavalactones are then biosynthesized by subsequent regio- and stereo-specific tailoring enzymes. We demonstrate the feasibility of engineering heterologous production of kavalactones and their derivatives in bacterial, yeast, and plant hosts, thus opening an avenue towards the development of new psychiatric therapeutics for anxiety disorders, which affect over 260 million people globally8.

scholarly journals De Novo Central Nervous System Processing of Myelin Antigen Is Required for the Initiation of Experimental Autoimmune Encephalomyelitis

2002 ◽  
Vol 168 (8) ◽  
pp. 4173-4183 ◽  
Author(s):  
Stephen Mark Tompkins ◽  
Josette Padilla ◽  
Mauro C. Dal Canto ◽  
Jenny P.-Y. Ting ◽  
Luc Van Kaer ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
De Novo ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals A case report of rare location of ganglioglioma

2019 ◽  
Vol 34 (1) ◽  
Author(s):  
Vikas Sharma ◽  
S. Bhaskar ◽  
Sumit Ramdas Hire ◽  
Arvind Ahuja
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Occipital Lobe ◽  
Cystic Mass ◽  
Mass Lesion ◽  
Occipital Region ◽  
Rare Tumors ◽  
Rare Location ◽  
The Central Nervous System

Abstract Background Gangliogliomas are rare tumors of the central nervous system. They can occur anywhere in the central nervous system but are most commonly located in the temporal lobe and are mainly found in children. Anaplastic ganglioglioma can result from either de novo or transformation of a pre-existing lesion. Case presentation We report a case of de novo anaplastic ganglioglioma in the parieto occipital region, which is a rare location. A 34-year-old lady presented with features of raised intracranial pressure (ICP) with right side hemiparesis. Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain showed well-defined intense heterogenously enhancing solid cystic mass lesion 5.3 × 5.2 cm in the left parieto occipital region with mass effect and midline shift. Intraoperatively, a cystic mass lesion with reddish brown nodule was seen in the left occipital lobe. Complete tumor excision was done. Microscopic and IHC examination was suggestive of anaplastic ganglioglioma. The post-operative period was uneventful. The patient received 60-Gy radiotherapy with temozolamide as adjuvant therapy, and repeat imaging showed no tumor recurrence. Conclusion Anaplastic gangliogliomas are rare tumors with parieto occipital as rare location.

scholarly journals Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine Compounds Compared to Dimethyl Fumarate

2020 ◽  
Vol 17 (3) ◽  
pp. 1142-1152 ◽  
Author(s):  
Karl E. Carlström ◽  
Praveen K. Chinthakindi ◽  
Belén Espinosa ◽  
Faiez Al Nimer ◽  
Elias S. J. Arnér ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo ◽  
Dimethyl Fumarate ◽  
The Novel ◽  
The Central Nervous System ◽  
Demyelinating Disorders ◽  
Target Effects

Abstract The Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine CH-3 was the most promising candidate and selected for further comparison in vivo and later an experimental model for traumatic brain injury (TBI). CH-3 and DMF displayed comparable capacity to activate Nrf2 and downstream transcripts in vitro, but with less off-target effects on HIF1 from CH-3. This was verified in cultured microglia and oligodendrocytes (OLs) and subsequently in vivo in rats. Following TBI, DMF lowered the number of leukocytes in blood and also decreased axonal degeneration. CH-3 preserved or increased the number of pre-myelinating OL. While both CH-3 and DMF activated Nrf2, CH-3 showed less off-target effects and displayed more selective OL associated effects. Further studies with Nrf2-acting compounds are promising candidates to explore potential myelin protective or regenerative effects in demyelinating disorders.

scholarly journals Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement

2016 ◽  
Vol 31 (9) ◽  
pp. 1114-1119 ◽  
Author(s):  
Leslie Hotchkiss ◽  
Sandra Donkervoort ◽  
Meganne E. Leach ◽  
Payam Mohassel ◽  
Diana X. Bharucha-Goebel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hereditary Spastic Paraplegia ◽  
De Novo ◽  
Central Nervous System Involvement ◽  
Spastic Paraplegia ◽  
De Novo Mutations ◽  
System Involvement

scholarly journals Neuroprotective profile of Piper Methysticum (Kava Kava) and its effects on the Central Nervous System: a systematic review

2020 ◽  
Vol 2 (1) ◽  
pp. 55-84
Author(s):  
Elaine Cristina Gurgel Andrade Pedrosa ◽  
Ana Paula Carvalho Bezerra ◽  
Ianara Mendonça da Costa ◽  
Francisco Irochima Pinheiro ◽  
Fausto Pierdoná Guzen
Keyword(s):  
Systematic Review ◽  
Central Nervous System ◽  
Nervous System ◽  
Piper Methysticum ◽  
System A ◽  
Kava Kava ◽  
The Central Nervous System

The 2016 revision of the WHO classification of tumours of the central nervous system

2017 ◽  
Author(s):  
Paul Kleihues ◽  
Elisabeth Rushing ◽  
Hiroko Ohgaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Who Classification ◽  
De Novo ◽  
Genetic Profiling ◽  
Primary Glioblastoma ◽  
System P ◽  
Significant Step ◽  
The Central Nervous System

The revised fourth edition of the WHO classification of Tumours of the Central Nervous System, published in 2016, comprises several newly recognized tumour entities, and a significant restructuring of the classification, mainly based on genetic profiling. Glioblastomas are now classified into two major types. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (primary glioblastoma IDH-wildtype) develops rapidly de novo without a recognizable precursor lesion. IDH-mutant glioblastoma (secondary glioblastoma IDH-mutant) develops more slowly through malignant progression from diffuse or anaplastic astrocytoma. Medulloblastomas are now defined by combining histological patterns (classic, desmoplastic/nodular, extensive nodularity, anaplastic) and genetic hallmarks (WNT-activated; SHH-activated, TP53-mutant; SHH-activated, TP53-wildtype; non-WNT/non-SHH). Other newly recognized tumour entities include diffuse midline glioma, H3 K27M-mutant; ependymoma, RELA fusion-positive; and embryonal tumour with multilayered rosettes. The new classification is a significant step forward and will facilitate the development of novel targeted therapies of brain tumours.

scholarly journals De novo primary central nervous system pure erythroid leukemia/sarcoma with t(1;16)(p31;q24) NFIA/CBFA2T3 translocation

Haematologica ◽  
2020 ◽  
Vol 105 (4) ◽  
pp. e194-e197 ◽  
Author(s):  
Huifei Liu ◽  
Terri L. Guinipero ◽  
Kathleen M. Schieffer ◽  
Chris Carter ◽  
Susan Colace ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
De Novo
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