Phenserine

• CAS: 101246-66-6
• Catalog Number: ACM101246666
• Category: Other Products
• Molecular Weight: 337.42
• Molecular Formula: C₂₀H₂₃N₃O₂

Case Study

Application of (-)-Phenserine Tartrate in Mitigating Neuroinflammation and Synaptic Damage in mTBI and AD Mouse Models

Lecca D, et al. Neurobiology of Disease, 2019, 130, 104528.

In a preclinical study evaluating (-)-Phenserine tartrate for neurological recovery, researchers administered the compound at clinically translatable doses (2.5 and 5.0 mg/kg, BID) in a weight-drop induced mild traumatic brain injury (mTBI) model in both wild-type (WT) and APP/PSEN1 transgenic mice. Phenserine treatment significantly reduced neurodegeneration, as indicated by decreased Fluoro-Jade C-positive cell counts in the hippocampus and cortex. Anti-inflammatory effects were demonstrated through lowered IBA1-immunoreactivity and reduced TNF-α/IBA1 co-localization, suggesting attenuation of microglial activation. Phenserine also mitigated astrocyte activation, as shown by reduced GFAP expression. Synaptic integrity was preserved, with full reversal of PSD-95+ dendritic spine loss and restoration of Synaptophysin immunoreactivity. Notably, hippocampal long-term potentiation (LTP), impaired by mTBI, was restored by Phenserine, linking structural preservation to functional recovery. Behavioral improvements were validated using Novel Object Recognition and Y-maze paradigms. These results underscore Phenserine's multifaceted neuroprotective actions-reducing programmed cell death, suppressing neuroinflammation, and preserving synaptic structure and function. Its efficacy in both WT and AD-prone models positions (-)-Phenserine tartrate as a promising therapeutic candidate for mTBI and related neurodegenerative conditions.

Phenserine for the Restoration of Cognitive Function in an ICV-STZ-Induced Alzheimer's Disease Model

Ponce-Lopez T, et al. Brain Research, 2011, 1426, 73-85.

In a rat model of sporadic Alzheimer's disease (AD) induced by intracerebroventricular (ICV) administration of streptozotocin (STZ, 3 mg/kg, twice), phenserine was evaluated for its potential to reverse memory deficits and modulate insulin-related kinase signaling. Two weeks post-STZ administration, Wistar rats underwent short- and long-term memory assessment using an autoshaping learning paradigm. Phenserine (1 mg/kg) was administered post-training to assess cognitive recovery. Western blot analysis was subsequently performed on dissected hippocampal and prefrontal cortex (PFC) tissues to quantify phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and total GSK3β expression. STZ-treated rats exhibited significant reductions in p-GSK3β and memory performance, indicative of insulin signaling dysfunction associated with AD pathology. Phenserine administration effectively restored memory function and significantly increased p-GSK3β levels in the hippocampus, although no change in total GSK3β was observed. Restoration of p-GSK3β suggests that phenserine may exert therapeutic effects by modulating GSK3β-mediated tau phosphorylation, a key factor in neurofibrillary tangle formation.

Application of (-)-Phenserine in Mitigating Neuronal Apoptosis Following Ischemia/Reperfusion Injury

Chang C-F, et al. Brain Research, 2017, 1677, 118-128.

(-)-Phenserine, a reversible acetylcholinesterase (AChE) inhibitor, was evaluated for its neuroprotective efficacy in ischemia/reperfusion (I/R) injury using both in vivo and in vitro models. In a rat middle cerebral artery occlusion (MCAO) model, intraperitoneal administration of (-)-phenserine significantly reduced cerebral infarct volume and improved behavioral outcomes. Concurrently, SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/RP) exhibited a dose-dependent inverted U-shaped survival response upon treatment with (-)-phenserine. Experimental analysis revealed that (-)-phenserine inhibited apoptosis by downregulating activated caspase-3, amyloid precursor protein (APP), MMP-9, and GFAP, while upregulating BDNF and Bcl-2 expression. Immunoblotting and histological staining confirmed these protein-level modulations. Mechanistic studies suggest that these effects are mediated via the ERK-1/2 signaling pathway. The comprehensive design incorporating both cellular and animal models demonstrated the compound's ability to mitigate neuronal loss in ischemic penumbra regions, highlighting its cholinergic and non-cholinergic protective actions.