scholarly journals Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer’s Disease, Parkinson’s Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 124
Author(s):  
Takumi Satoh ◽  
Dorit Trudler ◽  
Chang-Ki Oh ◽  
Stuart A. Lipton
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Nlrp3 Inflammasome ◽  
Carnosic Acid ◽  
Inflammasome Activation ◽  
Neuroprotective Effects ◽  
After Effects ◽  
The Brain

Rosemary (Rosmarinus officinalis [family Lamiaceae]), an herb of economic and gustatory repute, is employed in traditional medicines in many countries. Rosemary contains carnosic acid (CA) and carnosol (CS), abietane-type phenolic diterpenes, which account for most of its biological and pharmacological actions, although claims have also been made for contributions of another constituent, rosmarinic acid. This review focuses on the potential applications of CA and CS for Alzheimer’s disease (AD), Parkinson’s disease (PD), and coronavirus disease 2019 (COVID-19), in part via inhibition of the NLRP3 inflammasome. CA exerts antioxidant, anti-inflammatory, and neuroprotective effects via phase 2 enzyme induction initiated by activation of the KEAP1/NRF2 transcriptional pathway, which in turn attenuates NLRP3 activation. In addition, we propose that CA-related compounds may serve as therapeutics against the brain-related after-effects of SARS-CoV-2 infection, termed “long-COVID.” One factor that contributes to COVID-19 is cytokine storm emanating from macrophages as a result of unregulated inflammation in and around lung epithelial and endovascular cells. Additionally, neurological aftereffects such as anxiety and “brain fog” are becoming a major issue for both the pandemic and post-pandemic period. Many reports hold that unregulated NLRP3 inflammasome activation may potentially contribute to the severity of COVID-19 and its aftermath. It is therefore possible that suppression of NLRP3 inflammasome activity may prove efficacious against both acute lung disease and chronic neurological after-effects. Because CA has been shown to not only act systemically but also to penetrate the blood–brain barrier and reach the brain parenchyma to exert neuroprotective effects, we discuss the evidence that CA or rosemary extracts containing CA may represent an effective countermeasure against both acute and chronic pathological events initiated by SARS-CoV-2 infection as well as other chronic neurodegenerative diseases including AD and PD.

Neurodegenerative diseases and Flavonoids: Special reference to kaempferol

2021 ◽  
Vol 20 ◽  
Author(s):  
Rahul ◽  
Yasir Hasan Siddique
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neuroprotective Effects ◽  
Major Health Problem ◽  
Beneficial Effects

: Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington’s disease, Multiple Sclerosis and Ischemic stroke have become a major health problem worldwide. Pre-clinical studies have demonstrated the beneficial effects of flavonoids on neurodegenerative diseases and suggesting them to be used as therapeutic agents. Kaempferol is found in many plants such as tea, beans, broccoli,strawberriesand has neuroprotective effects against the development of many neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Huntington's disease. The present study summarizesthe neuroprotective effects of kaempferol in various models of neurodegenerative diseases. Kaempferol delays the initiation as well as the progression of neurodegenerative disorders by acting as a scavenger of free radicals and preserving the activity of various antioxidant enzymes. Kaempferolcan crossthe blood-brain barrier (BBB), and therefore results inan enhanced protective effect. The multi-target property of kaempferol makes it a potential dietary supplement in preventing and treating neurodegenerative diseases.

scholarly journals Bushen-Yizhi Formula Alleviates Neuroinflammation via Inhibiting NLRP3 Inflammasome Activation in a Mouse Model of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yousheng Mo ◽  
Erjin Xu ◽  
Renrong Wei ◽  
Baoluu Le ◽  
Lei Song ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Neuronal Degeneration ◽  
Interleukin 1 ◽  
Inflammasome Activation ◽  
Neuroprotective Effects ◽  
Nlrp3 Inflammasome Activation

Parkinson’s disease (PD), the second most common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Although the molecular mechanisms underlying dopaminergic neuronal degeneration in PD remain unclear, neuroinflammation is considered as the vital mediator in the pathogenesis and progression of PD. Bushen-Yizhi Formula (BSYZ), a traditional Chinese medicine, has been demonstrated to exert antineuroinflammation in our previous studies. However, it remains unclear whether BSYZ is effective for PD. Here, we sought to assess the neuroprotective effects and explore the underlying mechanisms of BSYZ in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine- (MPTP-) induced mouse model of PD. Our results indicate that BSYZ significantly alleviates the motor impairments and dopaminergic neuron degeneration of MPTP-treated mice. Furthermore, BSYZ remarkably attenuates microglia activation, inhibits NLPR3 activation, and decreases the levels of inflammatory cytokines in MPTP-induced mouse brain. Also, BSYZ inhibits NLRP3 activation and interleukin-1βproduction of the 1-methyl-4-phenyl-pyridinium (MPP+) stimulated BV-2 microglia cells. Taken together, our results indicate that BSYZ alleviates MPTP-induced neuroinflammation probably via inhibiting NLRP3 inflammasome activation in microglia. Collectively, BSYZ may be a potential therapeutic agent for PD and the related neurodegeneration diseases.

scholarly journals Clinicotherapeutic Potential of Leptin in Alzheimer’s Disease and Parkinson’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Soumyabrata Munshi ◽  
Vineet Kumar Khemka ◽  
Kalpita Banerjee ◽  
Sasanka Chakrabarti
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Peptide Hormone ◽  
The Elderly ◽  
Clinical Associations ◽  
The Brain

Chronic neurodegenerative diseases are a group of devastating neurological disorders that result in significant morbidity and mortality in the elderly population worldwide. Recent researches have shown some interesting associations of the classical antiobesity hormone leptin with two most important neurodegenerative diseases—Alzheimer’s disease (AD) and Parkinson’s disease (PD). Although several clinical studies have found the procognitive and memory-enhancing role of this peptide hormone in leptin-deficient patients, surprisingly it has not been used in any clinical trials involving patients with developing or full-blown neurodegenerative conditions. This review article is an attempt to bring together the existing information about the clinical associations of leptin with AD and PD. It starts with the basic understanding of leptin action in the brain and its derangements in these diseases and eventually discusses the potential of this hormone as a neuroprotective agent in clinical scenario.

scholarly journals Copper and zinc level alterations in the brain structures in Parkinson’s and Alzheimer’s diseases

2020 ◽  
Vol 9 (3) ◽  
pp. 21-26
Author(s):  
V.N. Salkov ◽  
R.M. Khudoerkov
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Brain Structures ◽  
Zinc Level ◽  
Copper And Zinc ◽  
Β Amyloid ◽  
High Concentrations ◽  
The Brain

The article reviews the literature on copper and zinc level alterations in the brain structures in neurodegenera-tive diseases (Parkinson's disease, PD, and Alzheimer's disease, AD). We discuss the ability of these micro-elements to bind to cellular proteins (α-synuclein in PD and β-amyloid in AD) disrupting their metabolism. The literature analysis shows that high copper levels in the neurons of nigrostriatal brain formations in PD initiate oxidative stress development. Copper extracellular deficiency disturbs iron metabolism and thus may increase the stress. Low zinc levels weaken the enzyme antioxidant potential. In AD, disruption of the homeostasis of these metals in the brain structures has a different effect. In the early stages, the complex formed by β-amyloid and copper (II) ions is involved in a series of redox reactions, resulting in the formation of free radicals which stimulate the expression of neuroinflammatory mediator, accompanied by uncontrolled release of zinc, high concentrations of which catalyzing the formation of the toxic forms of aggregated Aβ. Keywords: brain, copper, zinc, Parkinson’s disease, Alzheimer’s disease

scholarly journals Peroxisome Proliferator-Activated Receptors: A New Ray Of Hope For Parkinson’s Disease

2021 ◽  
Vol 9 (9) ◽  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Peroxisome Proliferator ◽  
Neuroprotective Effects ◽  
In Vivo Models ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

PD (PD) is a debilitating progressive age-related neurodegenerative disorder that negatively impacts bodily movement. It is the second most common type of neurodegenerative disease after Alzheimer's disease. Although the etiology and pathogenesis of PD remain unknown, a vast body of evidence indicates that oxidative stress, inflammation, apoptosis, mitochondrial dysfunction, and proteasomal dysfunction all play a role in the disease's pathogenesis. Because of the multifactorial nature of the disease, current drug treatment can only offer symptomatic relief and cannot stop or delay the disease progression. The Peroxisome proliferator-activated receptors (PPARs) are the member of the receptor’s superfamily called, nuclear receptors, regulates the growth, differentiation of the tissues, inflammation, mitochondrial function, wound healing, lipid metabolism, and glucose metabolism. Several PPAR agonists have recently been shown to protect neurons from oxidative damage, inflammation, and apoptosis in Alzheimer's disease, PD, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. We review the research on the neuroprotective effects of PPAR agonists in in-vitro and in-vivo models of PD in this paper. Similarly, the pharmacological mechanism of PPAR agonists' neuroprotective effects is examined. Finally, PPAR agonists exert neuroprotective effects by controlling the expression of a set of genes involved in cell survival processes, suggesting that they may be a potential therapeutic target in crippling neurodegenerative diseases like PD. Keywords: Parkinson’s disease, neuroprotective, neuro inflammatory, oxidative stress, PPAR agonist

Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

2020 ◽  
Vol 19 (3) ◽  
pp. 174-183
Author(s):  
Subrat Kumar Bhattamisra ◽  
Lee Yuen Shin ◽  
Hanis Izzati Binti Mohd Saad ◽  
Vikram Rao ◽  
Mayuren Candasamy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Insulin Signaling ◽  
Therapeutic Approaches ◽  
The Brain

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords “insulin”; “insulin resistance”; “Alzheimer’s disease”; “Parkinson’s disease” in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

scholarly journals The regulatory role of cystatin C in autophagy and neurodegeneration

2019 ◽  
Vol 23 (4) ◽  
pp. 390-397
Author(s):  
T. A. Korolenko ◽  
A. B. Shintyapina ◽  
A. B. Pupyshev ◽  
A. A. Akopyan ◽  
G. S. Russkikh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cystatin C ◽  
Transgenic Mouse Model ◽  
Parkinson’S Diseases ◽  
The Brain ◽  
Intraocular Fluid

Autophagy is a dynamic cellular process involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. It is particularly important in neurons, which do not have a proliferative option for cellular repair. Autophagy has been shown to be suppressed in the striatum of a transgenic mouse model of Parkinson’s disease. Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C. It has been suggested that cystatin C plays the primary role in amyloidogenesis and shows promise as a therapeutic agent for neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases). Cystatin C colocalizes with the amyloid β-protein in the brain during Alzheimer’s disease. Controlled expression of a cystatin C peptide has been proposed as a new approach to therapy for Alzheimer’s disease. In Parkinson’s disease, serum cystatin C levels can predict disease severity and cognitive dysfunction, although the exact involvement of cystatin C remains unclear. The aim: to study the role of cystatin C in neurodegeneration and evaluate the results in relation to the mechanism of autophagy. In our study on humans, a higher concentration of cystatin C was noted in cerebrospinal fluid than in serum; much lower concentrations were observed in other biological fluids (intraocular fluid, bile, and sweat). In elderly persons (61–80 years old compared to practically healthy people at 40–60 years of age), we revealed increased cystatin C levels both in serum and intraocular fluid. In an experiment on C57Bl/6J mice, cystatin C concentration was significantly higher in brain tissue than in the liver and spleen: an indication of an important function of this cysteine protease inhibitor in the brain. Using a transgenic mouse model of Parkinson’s disease (5 months old), we demonstrated a significant increase in osmotic susceptibility of brain lysosomes, depending on autophagy, while in a murine model of Alzheimer’s disease, this parameter did not differ from that in the appropriate control.

scholarly journals Control of Neuroinflammation through Radiation-Induced Microglial Changes

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2381
Author(s):  
Alexandra Boyd ◽  
Sarah Byrne ◽  
Ryan J. Middleton ◽  
Richard B. Banati ◽  
Guo-Jun Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Ionising Radiation ◽  
Neuroprotective Effects ◽  
Radiation Induced ◽  
The Central Nervous System ◽  
Inflammatory Molecules ◽  
Microglial Response

Microglia, the innate immune cells of the central nervous system, play a pivotal role in the modulation of neuroinflammation. Neuroinflammation has been implicated in many diseases of the CNS, including Alzheimer’s disease and Parkinson’s disease. It is well documented that microglial activation, initiated by a variety of stressors, can trigger a potentially destructive neuroinflammatory response via the release of pro-inflammatory molecules, and reactive oxygen and nitrogen species. However, the potential anti-inflammatory and neuroprotective effects that microglia are also thought to exhibit have been under-investigated. The application of ionising radiation at different doses and dose schedules may reveal novel methods for the control of microglial response to stressors, potentially highlighting avenues for treatment of neuroinflammation associated CNS disorders, such as Alzheimer’s disease and Parkinson’s disease. There remains a need to characterise the response of microglia to radiation, particularly low dose ionising radiation.

Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

2020 ◽  
Vol 18 (10) ◽  
pp. 758-768 ◽  
Author(s):  
Khadga Raj ◽  
Pooja Chawla ◽  
Shamsher Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Syndrome ◽  
Dopamine Synthesis ◽  
Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

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