Wnt Signaling Modulators Exhibit Neuroprotective Effects via Combating Astrogliosis and Balancing Synaptic Density at Early and Late Stage Temporal Lobe Epilepsy

Article

Author: Sandhu, Arushi ; Kumar, Anil ; Gautam, Vipasha ; Bhatia, Alka ; Sharma, Antika ; Saha, Lekha ; Rawat, Kajal

Temporal Lobe Epilepsy (TLE) is a severe neurological condition characterized by recurrent seizures that often do not respond well to available anti-seizure medications. TLE has been associated with epileptogenesis, a process that starts during the latent period following a neurologic insult and is followed by chronic phase. Recent research has linked canonical Wnt signaling to the pathophysiology of epileptogenesis and TLE. Our previous study demonstrated differential regulation of canonical Wnt signaling during early and late stage post status epilepticus (SE) induction. Building on these findings, our current study utilized Wnt modulators: GSK-3β inhibitor 6-bromoindirubin-3'-oxime (6-Bio) and disheveled inhibitor niclosamide and investigated their impact on canonical Wnt signaling during the early (30 days) and later stages (60 days) following SE induction. We assessed several parameters, including seizure frequency, astrogliosis, synaptic density, and neuronal counts in hippocampal tissue. We used immunohistochemistry and Nissl staining to evaluate gliosis, synaptic density, and neuronal counts in micro-dissected hippocampi. Western blotting was used to examine the expression of proteins involved in canonical Wnt/β-catenin signaling, and real-time PCR was conducted to analyze their relative mRNA expression. Wnt modulators, 6-Bio and Niclosamide were found to reduce seizure frequency and various other parameters including behavioral parameters, hippocampal morphology, astrogliosis and synaptic density at different stages of TLE.

01 Mar 2023·Pharmaceutical Patent Analyst

Riluzole and Its Prodrugs for the Treatment of Alzheimer’s Disease

Article

Author: Al-Horani, Rami A

Current medications for Alzheimer’s disease help manage symptoms and behavioral problems. Nevertheless, they do not slow the progression of cognitive decline or dementia. A potential approach for treating Alzheimer’s disease is to target neurons that are sensitive to disease pathobiology such as glutamatergic neurons. Several patents disclosed methods for treating Alzheimer’s disease by administering riluzole or its prodrugs. Clinical trials revealed that 6 months treatment using riluzole or troriluzole is associated with a slower decline in the tomographic measures of the positron emissions of cerebral glucose metabolism in Alzheimer’s patients. The proposed strategy claims to prevent and/or slow the cognitive decline of Alzheimer’s patients and to enhance global functioning. These claims may also pave the way for other glutamate modulators to be used for Alzheimer’s disease.

01 Oct 2021·Archives of Razi Institute

Role of Dopaminergic and Cannabinoidergic Receptors on Ghrelin-Induced Hypophagia in 5-Day-Old Broiler Chicken.

Article

Author: Zendehdel, M ; Asghari, A ; Farrokhi, R ; Gilanpour, H ; Babapour, V

The present study aimed to identify the role of dopaminergic and cannabinoidergic systems in the ghrelin-induced hypophagia among meat-type chickens. In the first experiment, intracerebroventricular (ICV) injection was applied to birds with control solution, D₁ receptor antagonist (5 nmol), ghrelin (6 nmol), and D1 receptor antagonist plus ghrelin. The second to sixth experiments were similar to the first one, with the difference that D₂ receptor antagonist (5 nmol), D₃ receptor antagonist (6.4 nmol), D₄ receptor antagonist (6 nmol), the precursor of dopamine (125 nmol), and 6-hydroxy dopamine (150 nmol) instead of D₁ antagonist were injected into the broiler chickens. In experiment 7, control solution and different levels of ghrelin antagonists (5, 10, and 20 nmol) were injected. In experiment 8, the chickens were ICV injected with control solution, ghrelin antagonist (10 nmol), dopamine (40 nmol), and ghrelin antagonist plus dopamine. In experiments 9 and 10, CB₁ and CB₂ receptors antagonist (6.25µg and 5µg) were co-injected with ghrelin (6 nmol), respectively, measuring the food intake for 120 min after the injection. It was observed that ghrelin ICV injection considerably reduced food intake, whereas ghrelin antagonist increased food intake, depending on the dose (P<0.05). In addition, ghrelin-induced hypophagia was significantly attenuated by D₁ receptor antagonist and 6-hydroxy dopamine (P<0.05), while the dopamine precursor considerably elevated the ghrelin-induced food intake (P<0.05). The dopamine-induced feeding behavior was diminished by the co-administration of [D-Lys-3]-GHRP-6 (10 nmol)+dopamine (40 nmol) (P<0.05). In addition, CB₁ receptor antagonists enhanced the ghrelin influence on food intake (P<0.05). The results implied that the hypophagic impact of ghrelin was probably mediated by D₁ and CB₁ receptors within neonatal broilers.

100 Deals associated with Ghrelin Modulators (7TM Pharma)

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Discovery	DK	7TM Pharma	01 Jul 2016

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