Motiva (nefiracetam) / Neuren - LARVOL DELTA

Ribo-ITP enables identification of translons from limited input samples. (PubMed, Nat Commun) - "Further, using a machine learning model, we predict that specific upstream translons in synaptically enriched mRNAs regulate translation efficiency of the annotated coding region. Taken together, we present a proof-of-concept study to identify non-canonical translation events from low input samples which can be applied to cell and tissue types inaccessible to conventional methods."

Journal

Yeast Rai1p and the RAC complex (Ssz1p/Zuo1p) modulate uORF-mediated GCN4 translational control under stress conditions. (PubMed, RNA) - "Translation reinitiation (REI) is one of the most important gene-specific regulatory mechanisms by which eukaryotic cells influence expression of main translons, for example during highly conserved integrated stress response (ISR)...We also explored interactomes of these proteins. Collectively, we present three previously unknown factors that co-regulate stress response to amino acid starvation in the budding yeast by unique mechanisms."

Journal

Mitochondrial translation termination, recycling, reinitiation, and rescue for in-frame and out-of-frame contexts. (PubMed, Nat Commun) - "Here, via high-resolution mitochondrial Ribo-Seq and Disome-Seq, we reveal: the specificity of release factors for different kinds of stop codons; the role of mtRF1 in vertebrates, which do not have noncanonical stop codons in their main translons; the recycling-coupled translation of internal translons; and the rescue of mitoribosomes in the early elongation stage...Moreover, HEMK1-mediated methylation of release factors enhances the termination reaction on stop codons. Our results provide insights into the mitoribosome dynamics that are associated with the completion of protein synthesis."

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Elongationless start-stop elements are stress-resilient translation gates that are more repressive than uTranslons. (PubMed, Nucleic Acids Res) - "This cycling explained increased ribosome retention at start-stops and was-in contrast to ribosome retention at uTranslons-independent of the global initiation state. Finally, we showed that the start-stop element in human ATF4 augments the core regulatory model by controlling translation of the uTranslons."

Journal • ATF4 • EIF1

The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides. (PubMed, EMBO J) - "What peptides do lncRNAs encode as true translons?...Shouldn't we coin the coding subset of lncRNAs its apt name: cryptic long non-coding RNAs (crpt-lncRNAs) for their cryptic coding capacity? These and other questions concerning these current winners of the spotlight in molecular biology, which await resolution, are discussed so that molecular history can be rewritten once again."

Journal • Review • Developmental Disorders

Human SRD5A1 as a case of gene expression indel-resistance in triple-coding region. (PubMed, Genome Biol) - "We argue for the importance of identification, characterisation and annotation of productive RNA translation irrespective of the presumed biological roles of its products."

Journal • SRD5A1

Semen Sojae Praeparatum ameliorates triptolide-induced liver injury by regulating bile acid homeostasis and the Keap1/Nrf2/p62 axis. (PubMed, Phytomedicine) - "SSP ameliorated TP-induced liver injury by modulating bile acid homeostasis and the Keap1/Nrf2/p62 pathway, thereby alleviating oxidative stress and excessive autophagy."

Journal • Hepatology • Liver Failure • KEAP1

Treatment of apathy in stroke patients: a systematic review. (PubMed, Front Neurol) - "Pharmacological interventions with escitalopram and donepezil (alone or combined with intensive language action therapy) showed potential benefits. Nefiracetam yielded mixed results depending on dose and coexisting depression...Nevertheless, evidence remains scarce and heterogeneous, underscoring the need for larger, high-quality randomized controlled trials to establish definitive treatment guidelines. https://www.crd.york.ac.uk/PROSPERO/view/CRD42022332559."

Clinical • Journal • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Depression • Hematological Disorders • Psychiatry

Translon: a single term for translated regions. (PubMed, Nat Methods) - No abstract available

Journal

Ribo-ITP expands the translatome of limited input samples. (PubMed, bioRxiv) - "Mutating the translons in mESCs identified a small proportion that negatively impacted growth. Taken together, we present a proof-of-concept study to identify non-canonical translation events from low input samples which can be applied to cell and tissue types inaccessible to conventional methods."

Journal

Translation complex profile sequencing allows discrimination of leaky scanning and reinitiation in upstream open reading frame-controlled translation. (PubMed, J Mol Biol) - "Upstream open reading frames (uORFs) are a class of translated regions (translons) in mRNA 5' leaders...Using several examples, we show how TCP-seq could be used to estimate both repressiveness and modes of action of individual uORFs. We demonstrate how this approach could be used to assess the mechanisms of uORF-mediated translation control in the mRNA of several human genes, including EIF5, IFRD1, MDM2, MIEF1, PPP1R15B, TAF7, and UCP2."

Journal • PPP1R15B

Ribosome decision graphs for the representation of eukaryotic RNA translation complexity. (PubMed, Genome Res) - "We termed the latter "translons." Nondeterministic events, such as initiation, reinitiation, selenocysteine insertion, or ribosomal frameshifting, are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions and for analyzing genetic variation and quantitative genome-wide data on translation for characterization of regulatory modulators of translation."

Journal

Discovery of Novel Pain Therapies Without Side-effects by Combining Targeted Mutagenesis and Phenotype-based Drug Screening in Larval Zebrafish. (PubMed, FASEB J) - "The successful identification of new drug combinations to prevent respiratory depression while preserving analgesia suggests that our drug discovery platform in larval zebrafish will substantially accelerate the identification of new opioid drugs with reduced morbidity and mortality. Our platform is also being leveraged to discover non-opioid pain killers with reduced side-effects."

Adverse events • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Infectious Disease • Novel Coronavirus Disease • Pain • Psychiatry

[VIRTUAL] Acute Onset Apathy in the Context of Malignancy: A Case Report (APA 2021) - "The consulting team recommended continuing preadmission dose of Duloxetine 60 mg daily with addition of Aripiprazole 2 mg daily for depression augmentation. Antidepressants, antipsychotics, acetylcholine esterase inhibitors, and nefiracetam have all been used in clinical trials but the strongest evidence exists for stimulant use. Currently there is an urgent need for studies specifically focusing on treating apathy due to brain tumors"

Clinical • Alzheimer's Disease • Brain Cancer • Cardiovascular • CNS Disorders • Dementia • Depression • Fatigue • Immunology • Lung Cancer • Major Depressive Disorder • Mood Disorders • Non Small Cell Lung Cancer • Oncology • Pain • Palliative care • Psychiatry • Schizophrenia • Solid Tumor

Pharmacological reversal of synaptic and network pathology in human MECP2-KO neurons and cortical organoids. (PubMed, EMBO Mol Med) - "Two lead compounds, Nefiracetam and PHA 543613, specifically reversed MECP2-knockout cytologic neuropathology. The capacity of these compounds to reverse neuropathologic phenotypes and networks in human models supports clinical studies for neurodevelopmental disorders in which MeCP2 deficiency is the predominant etiology."

Journal • CNS Disorders • Developmental Disorders • Movement Disorders • Psychiatry

Postreactivation mifepristone impairs generalization of strongly conditioned contextual fear memories. (PubMed, Learn Mem) - "We built on previous observations that systemic treatment with the nootropic nefiracetam potentiates cued fear memory destabilization to facilitate mifepristone-induced reconsolidation impairment. However, mifepristone did reduce freezing to a novel context. These observations suggest that strong and established contextual fear memories do undergo destabilization without the need for pharmacological facilitation, and that impairments in strong context fear memory reconsolidation can manifest as a reduction in generalization."

Journal

Identifying, characterizing and understanding Nefiracetam solid state forms: a potential antidementia drug. (PubMed, J Pharm Sci) - "These new forms were investigated from a structural and thermodynamic point of view to evaluate the possibility of using these forms in alternative formulations. Furthermore, their dissolution rate and solubility were compared."

Journal • CNS Disorders

Improving Nefiracetam Dissolution and Solubility Behavior Using a Cocrystallization Approach. (PubMed, Pharmaceutics) - "Three of which were obtained with the biocompatible cocrystallization agents citric acid, oxalic acid, and zinc chloride. These latter have been fully structurally and physically characterized and the solubility, dissolution rate, and stability were compared to that of the initial Active Pharmaceutical Ingredient (API)."

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Dopaminergic D1 receptor signalling is necessary, but not sufficient for cued fear memory destabilisation. (PubMed, Psychopharmacology (Berl)) - "The use of combination pharmacological treatment to stimulate memory destabilisation and impair reconsolidation has potential therapeutic benefits, without risking a maladaptive increase of fear."

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