Neuroprotective Properties of CDP-choline

Neuroprotective Properties of Citicoline

Citicoline is the name of the pharmaceutical product that chemically is cytidine-50-diphosphocholine (CDP-choline), which is identical to the natural precursor of phospholipid phosphatidylcholine. After administration, CDP-choline undergos quick hydrolysis and dephosphorylation to produce cytidine and choline, which then enter the brain separately and then are used to restore CDP-choline inside neurons. This, in turn, is believed to result in inhibition of phospholipid breakdown and acceleration of phospholipid resynthesis cruitial for membrane repair. Neuroprotective properties of CDP-choline has been reported in many preclinical models of brain ischaemia and trauma. The compound has offered marked neuroprotection in many in vitro and in vivo models of brain ischaemic and neurodegenerative diseases, including brain hypoxia, ischaemia and intracerebral haemorrhage, brain and spinal cord trauma, in vitro glutamate excitotoxicity and also in vivo amyloid toxicity. However, the mechanisms of this neuroprotection are still unknown. One major effect of citicoline is believed to be stimulation of the synthesis and increase in the level of phospholipids. The other mechanisms suggested to be involved in the neuroprotective effects of CDP-choline include inhibition of activation of phospholipase A2. The related effects comprise attenuation of the increase in hydroxyl radical synthesis, preventing loss of cardiolipin (an exclusive inner mitochondrial membrane phospholipid essential for electron transport, which is degraded in response to cellular insults and disrupts the mitochondrial respiratory chain). In aged rats, an increase in the brain level of platelet-activating factor (a bioactive phospholipid implicated in neuronal excitotoxic death) has also been noted. In rats, attenuation of mitogen-activated protein kinases and caspase activation have been observed after CDP-choline administration. Last, but not least, according to the most recent report, treatment with CDP-choline has been found to stimulate sirtuin-1 (SIRT1) protein levels in neurons, in circulating blood mononuclear cells and in the neurons. This effect seems to be of critical importance for neuroprotection in experimental stroke because sirtinol, a specific inhibitor of SIRT1 which, by itself, does not influence infarct volume, has been shown to abolish the neuroprotection offered by citicoline. Citicoline showed a potent synergistic effect with resveratrol (which is known to be a SIRT1 activator).

Neuroprotective Properties of Citicoline

cognitive enhancers

Cognitive enhancers competition

Pharmacological cognitive enhancement among non-ADHD individuals—A cross-sectional study in 15 countries

Psychoactive substance use aiming at increased performance at work or while studying, usually referred to as pharmacological cognitive enhancement (PCE), has been extensively researched in recent years. Tabele shows the perceived effect of the use of single substance (categories) on cognitive performance. When alcohol or benzodiazepines were used to directly or indirectly enhance cognitive performance at work or while studying, only few perceived an actual increase while half and a third, respectively, reported decreased performance following the use. According to the provided self-reports, modafinil had the best effect profile:

Cognitive enhancers

Perceived effect of substance use for cognitive enhancement among  participants . The substances in the graph are ordered from left to right based on the highest to lowest  perceived increase of cognitive performance following the substance use originally aimed at enhancement.
References: Pharmacological cognitive enhancement among non-ADHD individuals—Across-sectional study in 15 countries



Investigations into a new class of pharmacologically active drugs for improvement of physical and mental efficiency in people, called actoprotectors, were carried out under Professor Vladimir Vinogradov at the Military Medical Acad­emy (then Leningrad, USSR; now, St. Petersburg, Russia)’s Department of Pharmacology in the 1970s. This work resulted in the development of the first and most com­monly used actoprotector, bemitil (chemical structure: 2-eth­ylbenzimidazole hydrobromide; English-language literature: “bemithil”, “bemithyl” or “bemethyl”; also known as “bemactor” and “metaprot” in later publications). This achieve­ment earned Professor Vinogradov and his research group the State Prize of the USSR. Other actoprotectors subsequently were formulated as well, the most important of which, from the practical point of view is bromantane.
The first recipients of bemitil were Soviet cosmonaughts. Bemitil also was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow. Later, throughout the 1990s, it was used as a basic medicinal agent in almost all of the corps of the Soviet and then Russian armies. Notably, its administra­tion made it possible to increase soldiers’ endurance over long marches; in the Air Forces, Missile Troops, and Army Air Defense, it enhanced work capacity and stability to hypoxia; and in the Navy, it reinforced stability to hypoxia and, where applicable, high temperatures. The latter property, in fact, had  determined its wide use by the “limited contingent” of Soviet troops in Afghanistan. Bemitil enabled soldiers, including Spe­cial Forces, to effectively perform combat missions under both hypoxic and high-temperature conditions. Bemitil’s effective­ness for various types of activities was shown also in its en­hancement of the physical and mental capacities of rescue and other workers deployed in the wakes of the Chernobyl catastrophe (1986), the earthquakes in Armenia (1988), and the railway accidents in Bashkiria (1989) (Shabanov, 2009a). Bromantane also was employed in the Soviet and Russian armies, to shorten recovery times after strong physical exer­tion, though not as widely as bemitil.
After the disintegration of the USSR in 1991, the official manufacture and clinical use of bemitil was discontinued. However, owing to its wide-ranging pharmacological activity, high efficiency, and safety, its initial sports and military medi­cine applications have been extended widely to other branch­es of practical medicine. As for bromantane, its production continued after 1991, though its applications were limited, pri­marily, to sports medicine. Nowadays, bemitil is manufactured in Ukraine (commercial name: Antihot) and is widely used in preparing Ukrainian national sport teams for international competitions. Bromantane is manufactured in Russia (com­mercial name: Ladasten); since 1997, anti-doping regulations have prohibited its use in sports, though it has recently been utilized in the treatment of patients with asthenic and restless-asthenic frustration.


pharmacological properties of piracetam-like compounds

Pharmacological properties of piracetam-like compounds

CompoundIUPAC namePotencyDosageBioavailability (%)Half-life
Piracetam2-oxo-1-pyrrolidineacetamideLow50 to >300mg/kg/d (up to 37 g/d)~1004–5h
Oxiracetam2-(4-hydroxy-2-oxopyrrolidin-1-yl)acetamideMedium25–40mg/kg/d (up to 2.4 g/d)~753–6 h
PramiracetamN-[2-(dipropan-2-ylamino)ethyl]-2-(2-oxopyrrolidin-1-yl)acetamideMedium10–20mg/kg/d (1.2 g/d)~1002–8 h
Aniracetam1-[(4-methoxybenzoyl)]-2-pyrrolidinoneMedium12–25mg/kg/d (1.5g/d)~111–2.5 h
Phenylpiracetam2-(4-phenyl-2-oxopyrrolidin-1-yl)acetamideHigh 2.5–5mg/kg/d (up to 0.75 g/d)~1003–5 h
Levetiracetam(2S)-2-(2-oxopyrrolidin-1-yl)butanamideMedium20–60mg/kg/d (up to 3 g/d)~1006–8h
Brivaracetam(2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamideMedium10–25mg/kg/d (up to 1.4 g/d)~907–8 h
Seletracetam(2S)-2-[(4R)-4-(2,2-difluoroethenyl)-2-oxopyrrolidin-1-yl]butanamideHigh0.03–10mg/kg/d (up to 0. 6 g/d)>908 h
NefiracetamN-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamideMedium10–15mg/kg/d (up to 0.9 g/d)NA3–5 h
Fasoracetam(5R)-5-(piperidine-1-carbonyl) pyrrolidin-2-oneHigh100mg/d79–974–6.5 h
Rolziracetam2,6,7,8-tetrahydro-1H-pyrrolizine-3,5-dioneNANA~90<25 min

Properties of tianeptine

The neurobiological properties of tianeptine (Stablon)

Tianeptine is a  antidepressant that has drawn much attention, because this compound challenges traditional monoaminergic hypotheses of depression. It’s now acknowledged that the antidepressant actions of tianeptine, together with its remarkable clinical tolerance, can be attributed to its particular neurobiological properties. The involvement of glutamate in the mechanism of action of the antidepressant tianeptine is consistent with a well-developed preclinical literature demonstrating the key function of glutamate in the mechanism of altered neuroplasticity that underlies the symptoms of depression.
Depression is a complex, heterogeneous disorder, and the mechanisms underlying its pathogenesis are not that clear and are the subject of intensive investigation using pharmacological and genetic tools and animal models. The ‘monoamine hypothesis’ of depression, which involves imbalances in serotonergic, noradrenergic and possibly dopaminergic functions, has dominated notions and explanations of the pathophysiology of depression since the empirical discovery of the antidepressant properties of monoamine oxidase inhibitors and tricyclics about 50 years ago. Although the monoaminergic neurotransmitters serotonin (5-HT), norepinephrine and dopamine (DA) are undoubtedly involved, it is now recognized that monoamine deficits are only part of the story and are not sufficient on their own to explain the mechanism of action of antidepressants. In extension to the chemical hypothesis of depression, contemporary theories suggest that major depressive disorders may be associated not only with an imbalance of neurotransmitters and neuromodulators but also with an impairment of neuroplasticity and cellular resilience, and that antidepressant medications act by normalizing this impairment. The term neuroplasticity describes the ability of the adult and differentiated brain to adapt functionally and structurally to internal and external stimuli and is considered today as a feature of depressive illness. Brain regions that exhibit neuroplastic processes include the hippocampus, amygdala and prefrontal cortex, as they are reported to undergo structural changes in depression, and alterations in these brain regions affect emotions, perceptions, memory and cognitive function. The concept of a serotonergic deficit in depression is particularly challenged by the drug tianeptine, an antidepressant with structural similarities to the tricyclic antidepressant agents but with different pharmacological properties. The efficacy and tolerability of tianeptine are clearly demonstrated in depressed patients. However, the monoamine hypothesis cannot explain these properties. In fact, tianeptine has contributed greatly to our realization of the complexity of the etiology of depression, and to the complexity of central mechanisms triggered by antidepressants. Its mechanisms of action clearly challenge the hypothesis of an immediate modulation of monoamine axes to support the antidepressant actions. Rather, tianeptine triggers a cascade of cellular adaptations that ultimately will lead to the antidepressant efficacy. Among those sustained adaptations, increased phosphorylation of glutamate receptors subtypes in circumscribed brain region appears particularly interesting. Glutamate is the major excitatory neurotransmitter in the brain controlling synaptic excitability and plasticity in most brain circuits, including limbic pathways. Glutamatergic mechanisms are crucial in virtually all key functions perturbed in depressed states. In addition, glutamate is an essential participant in many forms of adaptive plasticity, including: learning and memory. The actions of tianeptine on the glutamatergic system offer new insights into how this compound may be useful in the treatment of depression.
The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation
Molecular Psychiatry (2010) 15, 237–249

Buy Amanita Mucsaria

New method for identification and determination of ibotenic acid, muscimol and muscarine

New method for identification and determination of ibotenic acid, muscimol.


The CE–ESI-MS/MS (capillary electrophoresis coupled with electrospraytandem mass spectrometry) method for the identification, separation and determination of mushroom toxins, namely ibotenic acid, muscimol and muscarine, was developed. It proved to be sensitive and thus useful for the real sample analysis with omitting the labor and time consuming pretreatment step. The CE–ESI-MS/MS method was applied on the spiked human urine. The analytical characteristics of the proposed method, such as limits of detection, linearity and repeatability of the peak area and the migration time, were evaluated. Developed method is sufficient for the determination and quantification of studied toxins in human urine after mushroom intoxication.
muscarine muscimol ibotenic acidSMLXL

amanita mushroomSMLXL

Chinese Herbal Medicine against Alzheimer’s Disease

Chinese Herbal Medicine against Alzheimer’s Disease

Alzheimer’s disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM).
Radix Ginseng Extracts
Radix Ginseng (Renshen) is one of the perennial plants, which are in genus Panax and family Araliaceae. Ginsenosides are believed to be the active compounds of ginseng herbs. Renshen can reinforce vital energy, as described in Sheng Nong’s Herbal Classic’ (100AD). More than 31 types of ginsenosides have been extracted and each possesses a variety of biological activities. A number of studies have shown that ginsenosides can prevent and treat Alzheimer’s disease via regulating neurite outgrowth and synaptic plasticity, neuroprotection, anti-inflammatory effects andregulation of Aβ production and β-secretase activity. Ginsenoside Rg1 can significantly reduce the level of Aβ in the hippocampus of AD model mice brains, reverse the load of Aβ plaques in the cerebral cortex and hippocampus, protect cholinergic neurons and synapses, and improve spatial learning and memory function. Rg1 can inhibit the activity of secretase through activation of the PKA/CREB signaling pathway. It can also a neuroprotective effect by inhibiting the apoptosis of neuron cells, increasing the activity of neurons and decreasing the release of lactate dehydrogenase (LDH), reducing the expression of cytochrome C and increase the ratio of Bcl-2/Bax. Other monomers extracted from Radix Ginseng, like ginsenosides Rg3 and Rb1, can protect neurons by inhibiting the inflammatory response and hyperphosphorylation of tau protein. Ginsenoside Rg3 can reduce the expression of cellular factors associated with inflammation in the hippocampus, like tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and cyclooxygnasis-2 (COX-2), so as to improve the defects of learning and memory in rats. Another study demonstrated the neuroprotective effects of ginsenoside Rb1 against Aβ1_42 toxicity in cultured cortical neurons; the mechanism may be associated with inhibiting of tau hyperphosphorylation, increasing the levels of phospho-Ser (473)-Akt and down-regulating GSK-3β activity by PI3K activation, as well as reversing the Aβ1_42 induced decrease in phosphorylation cyclic AMP response element binding (CREB) protein.
Radix Salviae Miltiorrhize (Salvia Miltiorrhiza Bunge) Extracts
The active components and monomers extracted from Radix Salviae miltiorrhizecae (Danshen) can be divided into two main categories according to their solubility: lipophilic compounds like Tanshinone IIA and hydrophilic compounds like Salvianolic acid B. Many of these active components and monomers have protective effects on neurons, and can be used to treat Alzheimer’s disease. Tanshinone IIA can increase the viability and reduce the number of apoptotic of PC-12 cells by PI3K/Akt activation and GSK3β phosphorylation. Tanshinone IIA can also protect neurons from regulating the activity of calpain via the Bcl-xl and P35/CDK5 signaling pathway. Oxidative stress may play an important role in the occurrence and development of AD; tanshinone IIA has been shown to protect against oxidative stress and cell death by significantly decreasing the activities of malondialdehyde (MDA) and superoxide dismutase (SOD), increasing the level of glutathione peroxidase (GSH-PX), reducing the intracellular reactive oxygen species (ROS) level and increasing the mitochondrial membrane potential, reducing the caspase-3 activity, cytochrome c translocation and increasing the ratio of Bcl-2/Bax in Aβ25_35-induced cortical neurons. Danshensu, a hydrophilic compound of Danshen, can act as a protector of AD via antioxidative stress; it can enhance heme oxygenase-1 (HO-1) expression to suppress 6-hydroxydopamine (6-OHDA)-induced oxidative damage via PI3K/Akt/Nrf2 signaling pathways. Other studies have shown that monomers extracted from Danshen like Salvianolic acid B, Tanshinone I, Dihydrotanshinone I have neuron protective effects. Salvianolic acid B can inhibit the uptake of calcium and reduce the release of LDH. Cryptotanshinone and Dihydrotanshinone I can act as the cholinesterase inhibitors.
Radix Scutellariae (Scutallaria Baicalensis Georgi) Extracts
The active components and monomers extracted from Radix Scutellariae (Huangqin), thedry root of Scutellaria baicalensis Georgi, such as baicalin, baicalein and other flavonoids, showed significant biological activities such as antioxidation, free radicals scavenging, anti-inflammation, antitumor, antimicrobial effect. Baicalin, the main flavonoid extracted from Radix Scutellariae, can interact with copper directly and inhibit Aβ1_42 aggregation, as well as decrease H2O2 production, so as to inhibit Aβ aggregation and protect neurons. Baicalin could ameliorate Aβ1-42 protein-induced cognitive dysfunction, attenuate glia activation, TNF-α and IL-6 expression in AD model mice, its mechanism may be related to the inhibition of the JAK2/ STAT3 signaling pathway. Baicalein, another flavonoid isolated from the roots of Radix Scutellariae, has been found in vivo and vitro to promote nonamyloidogenic processing of APP, thereby reducing Aβ production and improving cognitive performance by activating gama-aminobutyric acid A (GABAA) receptors. Baicalein can also break down the aggregated amyloid beta fibrils, and the effect is time and dose-dependent. Chen Y C and colleagues examined the protective mechanism of Baicalein on hydrogenperoxide (H2O2)-induced cell death in rat glioma C6 cells and found that it can inhibit the activity of caspase 3, 8 and 9, modulate the activation of ERKs and induce heme oxygenase-1 (HO-1) expression, so as to inhibit cell apoptosis.
Ginkgo Leaf (Folium Ginkgo) Extracts
Ginkgo bilobais one of the oldest living tree species on the planet. The standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, contains 24% flavonoid glycosides (containing quercetin, kaempferol, isorhamnetin, etc.), 6% terpenoids (in which 3.1% are ginkgolides A, B, C, and J and 2.9% is bilobalide), and 5–10% organic acids, EGb761 has been demonstrated to possess neuroprotective effects in the treatment and prevention of AD, and the mechanisms involve antioxidant activity, protective effects on mitochondrial function, anti-apoptotic effect, anti-inflammatory effect, and protective effects against amyloidogenesis and Aβ aggregation. However, clinical trials of Ginkgo biloba leaf extracts on AD produced very different results. One study enrolled 2854 participants and found that long-term use of standardized Ginkgo biloba extract did not reduce the risk of progression to Alzheimer’s disease compared to theplacebo. Another clinical trial implemented by Ihl R and colleagues  found that EGB761 can improve cognitive functioning, neuropsychiatric symptoms and functional abilities in AD. Systematic review and meta-analysis of efficacy and tolerability of Ginkgo biloba extract EGb 761 in dementia indicated that Ginkgo biloba extract has good clinical effect on mild and moderate Alzheimer’s disease, furthermore, it was well tolerated. The research of the mechanisms of Ginkgo biloba extract in the treatment of AD is also widespread. Jahanshahi and colleagues found that Ginkgo biloba extract may protect neuron cells, can significantly reduce the apoptosis of the cells in CA1, CA3 and dentate gyrus areas of hippocampus of rat. Ginkgo biloba extract also manifests anti-inflammation effects, can reduce the number of microglia, decrease the expression of inflammation associated cytokines such as tumor necrosis factor α (TNF-α), Chemokine CCL-2 and the transcription of both proinflammatory and antiinflammatory genes (TNF-α, IL-1β, CCL-2 and IL-10) was markedly decreased in the hippocampus, and improve the cognitive function and preserves synaptic structure proteins in AD model mice. Antioxidation is another effect of Ginkgo biloba extract. EGb761 may increase the levels of superoxide dismutase (SOD) and glutathione (GSH), reduce the level of malondialdehyde (MDA), the expression of Bax, cytochrome c and caspase-9/3 in hippocampus of rats.
Herba Epimedii (Epimedium Herb) Extracts
Herba Epimedii (Yinyanghuo) can improve the function of the nervous system. Icariin, one kind of flavonoid, is the main active ingredient extracted from Herba Epimedii. The therapeutic effects of icariin have been found to target the pathological basis of Alzheimer’s disease, such as β-amyloid proteins, phosphorylation of tau proteins, the apoptosis of neuron cells, oxidative stress and so on. Lan Zhang and colleagues found that Icariin can reduce the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the amyloid precursor protein (APP) and β-secretion, and thus improve learning and memory functions. Icariin can also increase the cell viability and decrease apoptosis in cultured rat pheochromocytoma PC12 cells induced by amyloid beta protein fragment 25-35(Aβ25_35), the mechanism may be associated with the activation of the PI3K/Akt signaling pathway, downregulation of proapoptotic factors Bax and Caspase3, and upregulation of antiapoptotic factor Bcl-2. Icariin may protect neurons by inhibiting oxidative stress and hyperphosphorylation of tau protein, as well as activating PI3K/Akt signaling pathway, resulting in an inhibitory effect on glycogen synthase kinase (GSK)-3β, which is an important kinase response for tau protein hyperphosphorylation in the development of AD, icariin also can attenuate LDH leakage, reduce GSH depletion, prevent DNA oxidation damage and inhibit subsequent activation of caspase-3 and p53. These effects may associated with its inhibitory effect on the JNK/p38 MAPK pathways. Phosphodiesterase-5 (PDE5) inhibitors have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer’s disease, Icariin acts as a PDE5 inhibitor and can decrease the levels of amyloid precursor protein (APP), Aβ1_40, Aβ1_42 and PDE5 mRNA and protein levels in the hippocampus and cortex of the AD model mice and thus improve learning and memory functions significantly, and the mechanism may be associated with the stimulation of the NO/cGMP signaling pathway.
Huperzia serrata Extracts
Huperzine A, derived from the Chinese herb the Huperzia serrata, is considered to be a reversible, selective inhibitor of acetylcholinesterase (AChE), and can be used for the treatment of Alzheimer’s disease. A large number of clinical studies, systematic reviews and meta-analyses have found that huperzine A can significantly improve memory, cognitive function and daily living abilities of patients with AD, without serious side effects. Recent studies have found that huperzine A not only acts as a cholinesterase inhibitor, but also involves other mechanisms. Chun-Yan Wang and colleagues found that huperzine A also has antioxidant effects that can increase ADAM10, decrease BACE1 and APP695 protein levels and reduce Aβ levels and Aβ burden, as well as increase the activity of α secreted enzyme in cerebral cortex and hippocampus of transgenic AD mice through activating of the Wnt/β-Catenin signaling pathway. By reducing the contents of iron element in the brain, Huperzine A can reduce the production of Aβ and hyperphosphorylation of tau protein in the cerebral cortex and hippocampus of transgenic AD mice. Another study found that huperzine A can promote hippocampal neurogenesis in adult mice, suggesting that huperzine A may improve hippocampus-dependent functions.
Curcuma Longa Extracts
Curcumin is derived from the herb Curcuma Longa, more commonly known as turmeric that is used in curries and other spicy dishes from India, Asia and the Middle East. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor.  The structure of curcumin is largely composed of a carbon chain linking two aryl groups. Researchers have found the phenolic OH groups attached to the aryl groups to be able to scavenge reactive oxygen species (ROS), contributing to its anti-oxidative effect.  Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer’s disease (AD). A growing body of evidence indicates that oxidative stress, free radicals, beta amyloid, cerebral deregulation caused by bio-metal toxicity and abnormal inflammatory reactions contribute to the key event in Alzheimer’s disease pathology.   In in vivo studies, oral administration of curcumin has resulted in the inhibition of Aβ deposition, Aβ oligomerization, and tau phosphorylation in the brains. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies.

Bacopa monnieri protects against Alzheimer's Disease

Bacopa monnieri protects against alzheimer’s disease

Bacopa monnieri (Brahmi or water hyssop), is a plant belonging to the family Scrophulariaceae, that has been used in the traditional system of Ayurvedic medicine. Practitioners of Ayurveda claim varying benefits from Bacopa, including improved cognitive functions, intelligence and memory. Bacopa is a widely used supplement generally considered to be safe. In clinical trials on cognitive function, Bacopa extract is often administered at 300 mg/day. Some Brahmi supplements are standardized to contain a certain percentage of bacosides, the components that are believed to be biologically active.
Alzheimer’s disease (AD) is a chronic neurodegenerative disease of undetermined etiology, seen in the elderly people (rarely before 60). Disease is characterized by the impairment of memory, cognitive abilities and vocabulary. The pathogenesis of AD is not completely unknown, but it looks like some  genes play an important role in AD: presenelin-1 (PSEN-1), amyloid precursor protein (APP), presenelin-2 (PSEN-2), and apolipoprotein E (APOE). There are 3 possible mechanisms AD developement: deposition of Aβ proteins, deposition of τ proteins in cytoplasm of neurons, and neuronal degeneration due to above 2 components. Bacopa is a nootropic due to its: antioxidant, cholinergic, anti-beta amyloid properties.
Many animal studies revealed that Bacopa extract has an antioxidant and free radical scavenging action. Early studies showed that Bacopa extract inhibits lipid peroxidation in prefrontal cortex, hippocampus, and striatum of rats. Some experiments demonstrate the cholinergic effects of Bacopa which are similar to the current treatments of Alzheimer’s disease like: donepezil, rivastigmine and galantamine. Administration of Bacopa extracts also increases cerebral blood flow and the expression of brain derived neurotrophic factor (BDNF) – marker of neuronal plasticity. Bacopa extracts also decreases the formation of amyloid fibrils. All Experiments strongly indicate the value of Brahmi as a promising agent in Alzheimer’s disease and other neurodegenerative disease.

Bacopa monnieri: a Plant growing in marshlands; b, c Plant morphology; d chemical structure of bacoside.

THC reverses aging processes in the brain

THC reverses brain aging processes

Memory and cognitive performance decreases with age. Scientists have long been looking for ways to slow down  this process. THC can reverse ageing processes. Treatment with tetrahydrocannabinol (THC)  can restore cognition functions  in old mice and induce molecular changes that make them more similar to young animals.  The researchers administered  THC  through an implanted minipump to three mice groups: young, mature, old and then conducted standard tests for cognition.   Research revealed that THC treatment abolished the performance deficits found in mature and old mice.
 Attention, in the young mice, the treatment had the opposite effect—
THC actually impaired their performance!
To discover precisely what effect the THC treatment has in old mice, the researchers examined the brain tissue and gene activity of the treated mice. The findings were surprising: the molecular signature no longer corresponded to that of old animals, but was instead very similar to that of young animals.  The number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability.
A. Bilkei-Gorzo et al., “A chronic low dose of 9-tetrahydrocannabinol (THC) restores cognitive function in old mice,” Nature Medicine, doi:10.1038/nm.4311, 2017

Caffeine protects against neurodegenerative disorders

Caffeine protects against neurodegenerative disorders

Enzyme called NMNAT2 (nicotinamide mononucleotide adenylyl transferase 2)  is a key neuronal maintenance factor that provides potent neuroprotection against neurological disorders: Alzheimer’s, Huntington’s, Parkinson’s diseases. There are two known mechanism of action of NMNAT2 : a protective function to guard neurons from stress and a “chaperone function” to combat misfolded proteins called tau, which accumulate in the brain as “plaques” due to aging. Misfolded proteins have been linked to neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases, as well as amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease. Alzheimer’s disease, the most common form of these disorders, affects over 5.4 million people in USA. Most importantly, increased level of NMNAT2 protects against neurological disorders. To identify molecules that can boost NMNAT2, reserchears developed a high-throughput screening platform to detect NMNAT2 levels in cortical neurons and tested 1280 chemical compounds to identify NMNAT2 modulators. 24 of them were shown to increase the production of NMNAT2 in the brain. One of the NMNAT2 positive modulators was caffeine, which also has been shown to improve memory function in mice genetically modified to produce high levels of misfolded tau proteins. To confirm the positive effect of caffeine, researchers administered caffeine to genetically modified mice with lower levels of NMNAT2. As a result, the mice began to produce the same levels of the enzyme as normal mice. An additional 13 compounds were identified as having potential to lower the production of NMNAT2. The are also important because understanding their role in the body could lead to new insights into how they may contribute to dementia.
Ali, Y. O. et al. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons. Sci. Rep. 7, 43846