Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression: a Pragmatic Head-to-head Open, Randomized Multicenter Study: The 9th Study of the Danish University Antidepressant Group (DUAG 9)

The goal is to study the effect of lithium compared to cariprazine in patients with depression in a bipolar disease.
The main question it aims to answer is:
Difference in change between the two groups from baseline to after 8 weeks treatment on Hamilton Ratings Scale for Depression, 6-item version (HDS-6)
Participants will be randomized to treatment with either lithium or cariprazin.
Will meet for interview and ratings 4 times during study period.
In two meetings, there will be made blood samples and ECG. At one meeting also a Urine sample.
Will be contacted for telephone interviews at 6 occasions.

Start Date13 Dec 2022

Sponsor / Collaborator

Aalborg University Hospital

NCT05423522

/ CompletedPhase 2

Prospective, Multicenter, First Part Randomized, Placebo-controlled, Parallel-group, Double-blind Period Followed by Open-label Trial Period to Evaluate Clinical Safety & Efficacy of NanoLithium® NP03 in Patients With Mild-to-severe Alzheimer's Disease: Proof-of-concept Study

This proof-of-concept study will assess safety, tolerance, and efficacy of NanoLithium® NP03 in patients with mild-to-severe Alzheimer's Disease (AD).

Start Date20 May 2022

Sponsor / Collaborator

Medesis Pharma SA

100 Clinical Results associated with BACE1 x GSK-3β

100 Translational Medicine associated with BACE1 x GSK-3β

0 Patents (Medical) associated with BACE1 x GSK-3β

125

Literatures (Medical) associated with BACE1 x GSK-3β

01 Jul 2025·Food and Chemical Toxicology

Montelukast's potential as a neuroprotective agent against acrylamide induced neurotoxicity: In vivo and computational modelling

Article

Author: Mani, Vasudevan ; Arfeen, Minhajul ; Alwesmi, Mai B ; Alkhamiss, Abdullah Saleh ; Alshammari, Abdulaziz Arif A

Tobacco consumption, a leading cause of over 8 million deaths annually, exposes individuals to acrylamide (ACY), a neurotoxin in cigarette smoke that disrupts neurotransmitter function and induces oxidative stress, contributing to neurodegeneration. This study evaluated neuroprotective potential of montelukast (MTLU), a leukotriene receptor antagonist with anti-inflammatory and antioxidant properties, against ACY-induced neurotoxicity. Cognitive performance was assessed using elevated plus maze, novel object recognition, and Y-maze tests over 14 days. Biomarkers associated with neurodegeneration (BACE1, GSK-3β, AChE), neuroinflammation (COX-2, PGE2, TNF-α, NF-κB), oxidative stress (GSH, MDA, CAT), and apoptosis (Bcl-2, Caspase-3, Bax) were analyzed. Histopathological analyses of brain tissues were conducted to examine structural damage, and computational studies provided additional support for selected in vivo findings. MTLU significantly ameliorated ACY-induced cognitive deficits and reduced levels of GSK-3β, AChE, COX-2, PGE2, TNF-α, NF-κB, MDA, Bax, and Caspase-3 while enhancing antioxidant defenses (GSH) and upregulating Bcl-2. Histopathological analysis confirmed reduced structural brain damage, and molecular docking indicated strong binding potential for MTLU with AChE, COX-2, GSK-3β, BACE-1, and Caspase-3. While these findings suggest a protective role for MTLU in mitigating ACY-induced cognitive impairments, oxidative stress, neuroinflammation, and apoptosis, further research is needed to confirm its therapeutic potential and clinical relevance.

01 Mar 2025·Chemistry & Biodiversity

In Silico and In Vitro Evaluation of Quinoline Derivatives as Potential Inhibitors of AChE, BACE1, and GSK3β for Neurodegenerative Diseases Treatment

Article

Author: Assis de Oliveira, Bruno ; Glanzmann, Nícolas ; Mendonça de Assis, Pollyana ; Gonçalves de Oliveira, Filipe ; Rezende Barbosa Raposo, Nádia ; Zabala Capriles Goliatt, Priscila Vanessa ; de Assis Cruz, Otávio ; David da Silva, Adilson

AbstractNeurodegenerative diseases are characterized by the structural and functional loss of neurons, which impacts populations worldwide. Enzymes such as acetylcholinesterase (AChE), beta‐site APP cleaving enzyme‐1 (BACE1), and glycogen synthase kinase 3‐beta (GSK3β) are implicated in their progression. Therefore, developing compounds that inhibit these enzymes is relevant for treating these conditions. This study investigated the potential of quinoline analogs as multitarget enzyme inhibitors through in silico and in vitro assays. In silico analyses highlighted one of the derivatives as the most potent inhibitor for all proteins. In vitro assays confirmed that the quinoline derivatives modulated the activity of the three targets. The best derivative in silico also exhibited significant AChE inhibition of 94.6 %. For GSK3β and BACE1, four derivatives, with quinoline linked to the sulfonamide nitrogen, showed inhibition values above 40 %. Two of them demonstrated no cytotoxicity for human glioblastoma cell proliferation, and the most potent was noncytotoxic at 7.8 and 3.9 μg mL−1. In murine fibroblasts, the most potent derivative showed no cytotoxicity, unlike its effect on glioblastoma cells. Similarly, other derivatives were noncytotoxic at concentrations less than 62.5 μg mL−1. These findings highlight one of the derivatives as promising multitarget enzyme inhibitors for the treatment of neurodegenerative diseases.

28 Feb 2025·BioScience Trends

<i>N<sup>5</sup></i>-((perfluorophenyl)amino)glutamine regulates BACE1, tau phosphorylation, synaptic function, and neuroinflammation in Alzheimer's disease models

Article

Author: Kim, Sung Hyun ; Lee, Jeongmi ; Kim, Tai Kyoung ; Park, Sang Yoon ; Han, Sukmin ; Lee, Yujeong ; Cho, Heewon ; Cho, Yongeun ; Kim, Hyunwook ; Im, Jeonghyeong ; Kim, Jun-Sik ; Jeon, Yeji ; Jo, Dong-Gyu ; Chae, Minshik ; Yim, Joung Han ; Lee, Yeongyeong ; Hong, Ju-Mi

Alzheimer's disease (AD) is the most common type of dementia. Its incidence is rising rapidly as the global population ages, leading to a significant social and economic burden. AD involves complex pathologies, including amyloid plaque accumulation, synaptic dysfunction, and neuroinflammation. This study explores the therapeutic potential of N ⁵ -((perfluorophenyl)amino)glutamine (RA-PF), a derivative of γ-glutamyl-N'-(2-hydroxyphenyl)hydrazide (Ramalin), a compound with antioxidant and anti-inflammatory properties. Administration of RA-PF to 5xFAD mice decreases BACE1, reduces Aβ plaque deposition, inhibits microglial activation, restores synaptic transmission, and improves mitochondrial motility, leading to the recovery of cognitive function. Additionally, RA-PF treatment in 3xTg-AD mice alleviates anxiety-like behaviors, tau phosphorylation via inactivating GSK-3β, and BACE1 expression. Further transcriptomic analysis reveals RA-PF treatment in AD mice models recovers phagosome, inflammation, NOD-like receptor, presynaptic membrane, and postsynaptic membrane related signaling pathways. These findings suggest that RA-PF effectively targets multiple aspects of AD pathology, offering a novel multi-target approach for AD treatment.

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