Huperzine A: A promising anticonvulsant, disease modifying, and memory enhancing treatment option in Alzheimer’s disease

Damar, Ugur; Gersner, Roman; Johnstone, Joshua T.; Schachter, Steven C.; Rotenberg, Alexander

doi:10.1016/j.mehy.2016.12.006

Cited by 38 publications

(29 citation statements)

References 90 publications

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“…Moreover, new evidence indicates that in the early stages of AD, seizures and network hyperexcitability may appear and contribute to the development of early-onset AD by accelerating the development of cognitive impairment [ 24 , 121 , 122 ]. The use of various antiepileptic drugs in the prevention of cognitive deterioration in patients [ 123 , 124 , 125 ] and animal models with AD [ 23 , 126 ] also supports this argument, although data in patients are limited. A case-control study of patients with seizures and AD that were treated with levetiracetam, lamotrigine, or phenobarbital showed that levetiracetam caused fewer adverse events than the other antiepileptic drugs while phenobarbital produced persistent negative cognitive side effects [ 124 ].…”

Section: Ad and Seizuresmentioning

confidence: 99%

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Sánchez

García-Cabrero

Sánchez-Elexpuru

et al. 2018

IJMS

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Patients with dementia present epilepsy more frequently than the general population. Seizures are more common in patients with Alzheimer’s disease (AD), dementia with Lewy bodies (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) than in other dementias. Missense mutations in the microtubule associated protein tau (MAPT) gene have been found to cause familial FTD and PSP, while the P301S mutation in MAPT has been associated with early-onset fast progressive dementia and the presence of seizures. Brains of patients with AD, LBD, FTD and PSP show hyperphosphorylated tau aggregates, amyloid-β plaques and neuropil threads. Increasing evidence suggests the existence of overlapping mechanisms related to the generation of network hyperexcitability and cognitive decline. Neuronal overexpression of tau with various mutations found in FTD with parkinsonism-linked to chromosome 17 (FTDP-17) in mice produces epileptic activity. On the other hand, the use of certain antiepileptic drugs in animal models with AD prevents cognitive impairment. Further efforts should be made to search for plausible common targets for both conditions. Moreover, attempts should also be made to evaluate the use of drugs targeting tau and amyloid-β as suitable pharmacological interventions in epileptic disorders. The diagnosis of dementia and epilepsy in early stages of those diseases may be helpful for the initiation of treatments that could prevent the generation of epileptic activity and cognitive deterioration.

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Section: Ad and Seizuresmentioning

confidence: 99%

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Sánchez

García-Cabrero

Sánchez-Elexpuru

et al. 2018

IJMS

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“…In the past few decades, it has been observed that drugs such as donepezil [4] and Huperzine A [5] could alleviate distinct symptoms associated with AD. However, there are still no drugs that can retard the progression of AD.…”

Section: Introductionmentioning

confidence: 99%

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Wang

Liu

et al. 2020

J of Separation Science

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As a well-known traditional Chinese medicine formula, Ding-Zhi-Xiao-Wan has long been used for the routine treatment of Alzheimer's disease. However, the mechanism of Ding-Zhi-Xiao-Wan in treating Alzheimer's disease is unclear. Therefore, a nontargeted metabolomics method based on ultrahigh performance liquid chromatography with quadrupole time-of-flight mass spectrometry has been established to explore the metabolic variations in the urine of Alzheimer's disease rats and investigate the therapeutic mechanism of Ding-Zhi-Xiao-Wan on Alzheimer's disease. To develop a better rat model of Alzheimer's disease, amyloid β25-35 was injected into the bilateral hippocampus of Sprague-Dawley rats. Multivariate analysis approaches were applied to differentiate the urine components between the four groups. Thereafter, a targeted metabolomics method was used to verify the identified endogenous metabolites and determine the mechanism of action of Ding-Zhi-Xiao-Wan. Altogether, 26 potential biomarkers were found, of which 15 biomarkers (10 of which are potential biomarkers found in nontargeted metabolomics) were identified. The results show that Ding-Zhi-Xiao-Wan mainly affects the pathways of taurine and hypotaurine metabolism, tryptophan metabolism, and phenylalanine metabolism. Ding-Zhi-Xiao-Wan might play a role in the treatment of Alzheimer's disease by mediating antioxidative stress, regulation of energy metabolism, improvement of intestinal microbes, and protection of nerve cells.

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“…Huperzine A combines tetrameric AChE (G4) and indirectly activates both muscarinic and nicotinic types of AChRs (Wang et al, 2010 ). Moreover, the obvious overlap of tetrameric AChE and α7nAChRs in the hypothalamus, hippocampus, amygdale, cerebral cortex and midbrain of humans and rats (reviewed by Damar et al, 2017 ) indicates that cholinergic anti-inflammatory effects occur mainly via α7nAChRs in glial and neuronal cells (Pavlov and Tracey, 2006 ; Wang et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses

Ruan

Zhang

et al. 2018

Front. Aging Neurosci.

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Presbycusis (age-related hearing loss) is a potential risk factor for tinnitus and cognitive deterioration, which result in poor life quality. Presbycusis-related tinnitus with cognitive impairment is a common phenotype in the elderly population. In these individuals, the central auditory system shows similar pathophysiological alterations as those observed in Alzheimer’s disease (AD), including cholinergic hypofunction, epileptiform-like network synchronization, chronic inflammation, and reduced GABAergic inhibition and neural plasticity. Observations from experimental rodent models indicate that recovery of cholinergic function can improve memory and other cognitive functions via acetylcholine-mediated GABAergic inhibition enhancement, nicotinic acetylcholine receptor (nAChR)-mediated anti-inflammation, glial activation inhibition and neurovascular protection. The loss of cholinergic innervation of various brain structures may provide a common link between tinnitus seen in presbycusis-related tinnitus and age-related cognitive impairment. We hypothesize a key component of the condition is the withdrawal of cholinergic input to a subtype of GABAergic inhibitory interneuron, neuropeptide Y (NPY) neurogliaform cells. Cholinergic denervation might not only cause the degeneration of NPY neurogliaform cells, but may also result in decreased AChR activation in GABAergic inhibitory interneurons. This, in turn, would lead to reduced GABA release and inhibitory regulation of neural networks. Reduced nAChR-mediated anti-inflammation due to the loss of nicotinic innervation might lead to the transformation of glial cells and release of inflammatory mediators, lowering the buffering of extracellular potassium and glutamate metabolism. Further research will provide evidence for the recovery of cholinergic function with the use of cholinergic input enhancement alone or in combination with other rehabilitative interventions to reestablish inhibitory regulation mechanisms of involved neural networks for presbycusis-related tinnitus with cognitive impairment.

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Huperzine A: A promising anticonvulsant, disease modifying, and memory enhancing treatment option in Alzheimer’s disease

Cited by 38 publications

References 90 publications

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

Tau-Induced Pathology in Epilepsy and Dementia: Notions from Patients and Animal Models

A metabolomic study of the urine of rats with Alzheimer's disease and the efficacy of Ding‐Zhi‐Xiao‐Wan on the afflicted rats

Cholinergic Hypofunction in Presbycusis-Related Tinnitus With Cognitive Function Impairment: Emerging Hypotheses

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