The combination of acyclovir and dexamethasone protects against Alzheimer's disease-related cognitive impairments in mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease. However, effective drugs for this disease have not yet been developed. The analysis of big data indicated that childhood herpes virus infection may be associated with the incidence of AD, suggesting that anti-herpetic drugs, such as acyclovir, may have preventive and suppressive effects in AD therapy.

Substantial Neuroprotective and Neurite Outgrowth-Promoting Activities by Bis(propyl)-cognitin via the Activation of Alpha7-nAChR, a Promising Anti-Alzheimer's Dimer.

The cause of Alzheimer's disease (AD) could be ascribed to the progressive loss of functional neurons in the brain, and hence, agents with neuroprotection and neurite outgrowth-promoting activities that allow for the replacement of lost neurons may have significant therapeutic value. In the current study, the neuroprotective and the neurite outgrowth-promoting activities and molecular mechanisms of bis(propyl)-cognitin (B3C), a multifunctional anti-AD dimer, were investigated. Briefly, B3C (24 h pretreatment) fully protected against glutamate-induced neuronal death in primary cerebellar granule neurons with an IC50 value of 0.

Robust Neuritogenesis-Promoting Activity by Bis(heptyl)-Cognitin Through the Activation of alpha7-Nicotinic Acetylcholine Receptor/ERK Pathway.

Aims: Neurodegenerative disorders are caused by progressive neuronal loss in the brain, and hence, compounds that could promote neuritogenesis may have therapeutic values. In this study, the effects of bis(heptyl)-cognitin (B7C), a multifunctional dimer, on neurite outgrowth were investigated in both PC12 cells and primary cortical neurons.

Methods: Immunocytochemical staining was used to evaluate the proneuritogenesis effects, and Western blot and short hairpin RNA assays were applied to explore the underlying mechanisms.

Inhibiting β-amyloid-associated Alzheimer's pathogenesis in vitro and in vivo by a multifunctional dimeric bis(12)-hupyridone derived from its natural analogue.

Fibrillar aggregates of β-amyloid protein (Aβ) is the main constituent of senile plaques and considered to be one of the causative events in the pathogenesis of Alzheimer's disease (AD). Compounds that could inhibit the formation of Aβ fibrils and block Aβ fibrils-associated toxicity may have therapeutic potential to combat AD. Bis(12)-hupyridone (B12H) is a multifunctional homodimer derived from huperzine A, which is an anti-AD drug in China.

Sunitinib produces neuroprotective effect via inhibiting nitric oxide overproduction.

Background: Sunitinib is an inhibitor of the multiple receptor tyrosine kinases (RTKs) for cancer therapy. Some sunitinib analogues could prevent neuronal death induced by various neurotoxins. However, the neuroprotective effects of sunitinib have not been reported.

Substantial neuroprotection against K+ deprivation-induced apoptosis in primary cerebellar granule neurons by novel dimer bis(propyl)-cognitin via the activation of VEGFR-2 signaling pathway.

Background: Neuronal loss via apoptosis in CNS is the fundamental mechanism underlying various neurodegenerative diseases. Compounds with antiapoptotic property might have therapeutic effects for these diseases. In this study, bis(propyl)-cognitin (B3C), a novel dimer that possesses anti-AChE and anti-N-methyl-d-aspartate receptor activities, was investigated for its neuroprotective effect on K(+) deprivation-induced apoptosis in cerebellar granule neurons (CGNs).

Bis(propyl)-cognitin protects against glutamate-induced neuro-excitotoxicity via concurrent regulation of NO, MAPK/ERK and PI3-K/Akt/GSK3β pathways.

We have previously reported that bis(propyl)-cognitin (B3C), similar to memantine (MEM), is an uncompetitive N-methyl-d-aspartate receptor antagonist with fast off-rate property. In the current study, we further demonstrated that in primary cultures of rat cerebellar granule neurons (CGNs), 2h pretreatment of B3C (IC50, 0.45μM) prevented glutamate-induced excitotoxicity 10 times more potently than memantine (IC50, 4.

Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice.

Bis(12)-hupyridone, a novel multifunctional dimer, promotes neuronal differentiation more potently than its monomeric natural analog huperzine A possibly through α7 nAChR.

The cause of many neurodegenerative disorders can be ascribed to the loss of functional neurons, and thus agents capable of promoting neuronal differentiation may have therapeutic benefits to patients of these disorders. In this study, the effects and underlying mechanisms of bis(12)-hupyridone (B12H), a novel dimeric acetylcholinesterase inhibitor modified from huperzine A (HA), on neuronal differentiation were investigated using both the rat PC12 pheochromocytoma cell line and adult rat hippocampus neural stem cells. B12H (3-30 μM), characterized by morphological changes and expression of GAP-43, induced neurite outgrowth in a concentration- and time-dependent manner, with almost 3-fold higher efficacy than that of HA in PC12 cells.