An overview of systematic reviews of acupuncture for neurodegenerative disease.

BACKGROUND: Acupuncture has been widely used in the treatment of neurodegenerative diseases and a large number of systematic reviews (SRs) have been published, but the results are controversial. Therefore, it is necessary to comprehensively summarize and objectively evaluate the clinical evidence of acupuncture for neurodegenerative diseases. OBJECTIVE: To evaluate the SRs that assess the efficacy and safety of acupuncture for neurodegenerative diseases. This overview is intended to provide evidence for clinical decision making by healthcare providers and policymakers and to provide evidence for clinical decision making by healthcare providers and policymakers and to provide recommendations for researchers to conduct high quality SRs and clinical studies. METHODS: We searched four Chinese databases (SinoMed, CNKI, Wanfang and VIP) and four international databases (Cochrane Library, Embase, PubMed and Web of Science) for SRs of acupuncture for neurodegenerative diseases. The search period ran from the beginning of the database to March 5, 2023. Literature screening and data extraction were performed independently by two individuals. Methodological quality, risk of bias and associated evidence levels were assessed for all SRs using AMSTER 2, ROBIS and GRADE tools. In addition, the RCT overlap between SRs was calculated by corrected coverage area (CCA). We also conducted quantitative synthesis or descriptive analysis of the relevant data. RESULTS: Finally, we identified 53 SRs (three were qualitative descriptions and fifty were meta-analyses). Under AMSTAR 2, only one SR was rated as moderate quality, six SRs as low quality and 46 SRs as very low quality. According to ROBIS, 33 SRs were rated as a high risk of bias and 20 as a low risk of bias. Cognitive functions in neurodegenerative diseases, activities of daily living and the motor and non-motor outcomes associated with PD were included to summary description. The pooled results show that acupuncture combined with conventional treatment may have an overall advantage over conventional treatment, but the quality of evidence is low. Specific adverse reactions/events were reported in 20 SRs. Common needle-related adverse events included pain, dizziness, bleeding, or subcutaneous hematoma. No severe adverse events were reported in any SRs. CONCLUSION: Evidence suggests that acupuncture is generally effective and relatively safe for cognitive function and activities of daily living in neurodegenerative diseases. In addition, acupuncture may have some benefits in improving motor and non-motor symptoms in patients with PD. However, high-quality RCTs and SRs are still needed to further clarify the efficacy and safety of acupuncture in treating neurodegenerative diseases.

The potential of hyperbaric oxygen as a therapy for neurodegenerative diseases.

The World Health Organization estimates that by the year 2040, neurodegenerative diseases will be the second leading cause of death in developed countries, overtaking cancer-related deaths and exceeded only by cardiovascular disease-related death. The search for interventions has therefore become paramount to alleviate some of this burden. Based on pathways affected in neurodegenerative diseases, hyperbaric oxygen treatment (HBOT) could be a good candidate. This therapy has been used for the past 50 years for conditions such as decompression sickness and wound healing and has been shown to have promising effects in conditions associated with neurodegeneration and functional impairments. The goal of this review was to explore the history of hyperbaric oxygen therapy, its uses, and benefits, and to evaluate its effectiveness as an intervention in treating neurodegenerative diseases. Additionally, we examined common mechanisms underlying the effects of HBOT in different neurodegenerative diseases, with a special emphasis on epigenetics.

Benefits of Tai Chi Quan on neurodegenerative diseases: A systematic review.

BACKGROUND: Neurodegenerative diseases have become an important concern with the accelerated aging process. Tai Chi Quan (TCQ) has positive benefits for brain health and chronic diseases. The aim of this study was to summarize the protective effects of TCQ for motor function, cognition, quality of life, and mood in patients with neurodegenerative diseases. METHODS: A systematic search was conducted via PubMed database and the Web of Science core collection database until August 20, 2021. The available English systematic reviews, meta-analyses, and clinical trials were included. Two reviewers completed the screening and assessment process independently. RESULTS: A total of 28 studies on Parkinson's disease, 21 on cognitive impairment, and 9 on multiple sclerosis met the included criteria. The study found that TCQ remarkably improved general motor function and balance, and prevented falls for Parkinson's disease. TCQ significantly improved global cognitive function for cognitive impairment. TCQ was likely safe and beneficial for multiple sclerosis as result of heterogeneous outcomes and small samples. CONCLUSION: TCQ exercise can effectively improve the motor function, global cognitive function, and falls in patients with neurodegenerative diseases. However, the positive effects of TCQ on the quality of life and mood of patients with neurodegenerative diseases need further evidence.

The effectiveness of aromatherapy and reflexology in neurodegenerative disorders: a systematic review and meta-analysis.

Many neurodegenerative conditions are chronic disorders and result in a range of debilitating symptoms, with many people turning to complementary therapies. A systematic review and meta-analysis were conducted to investigate the evidence on effectiveness of aromatherapy and reflexology on all neurodegenerative conditions. We identified nine eligible studies (total sample n = 504 participants) all of which were on multiple sclerosis only. A meta-analysis was conducted including data from six studies, which demonstrated no significant benefit of aromatherapy/reflexology; however, the sample sizes were small and of low quality. This systematic review confirmed that it is not possible to draw conclusions regarding the effectiveness of reflexology and aromatherapy in multiple sclerosis. Larger high-quality studies are required to test these widely used therapies.

Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling.

The development of cell reprogramming technologies became a breakthrough in the creation of new models of human diseases, including neurodegenerative pathologies. The iPSCs-based models allow for the studying of both hereditary and sporadic cases of pathologies and produce deep insight into the molecular mechanisms underlying neurodegeneration. The use of the cells most vulnerable to a particular pathology makes it possible to identify specific pathological mechanisms and greatly facilitates the task of selecting the most effective drugs. To date, a large number of studies on patient-specific models of neurodegenerative diseases has been accumulated. In this review, we focused on the alterations of such a ubiquitous and important intracellular regulatory pathway as calcium signaling. Here, we reviewed and analyzed the data obtained from iPSCs-based models of different neurodegenerative disorders that demonstrated aberrant calcium signaling.

Medicinal Plants for Anti-neurodegenerative diseases in West Africa.

ETHNOPHARMACOLOGICAL RELEVANCE: Neurodegenerative diseases are neuronal diseases that affect the brain components by degenerating the structure and function of the central or peripheral nervous system progressively. It is a leading cause of death and affects huge amount of people worldwide. Plant-based medicines have been utilised in the therapies for many illnesses that have defied western treatments, including neurodegenerative diseases. AIM OF THIS REVIEW: This review presents an overview of the major neurodegenerative diseases and reported prominent medicinal plants used in managing those diseases in West Africa. METHODS: Scientific articles regarding medicinal plants and their usefulness in managing neurodegenerative diseases in West Africa were pooled from different scientific databases. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to filter articles based on their relevance. Pharmacological activity, plant parts used, experimental models, and some isolated chemical compounds of those plants were summarised. RESULTS: In the West Africa region, Fabaceae (19%) and Solanaceae (13%) have the highest representation of plant families used to treat neurological diseases, while Apocynaceae, Asteraceae, Euphorbiaceae have also been utilised. Flavonoids, alkaloids, phenolic compounds, terpenoids, coumarins present in those plants and their derivatives are reported to possess neuro-protective effects. Biochemical enzymes correlating to antioxidants, anti-inflammatory effects are the potential targets against neurodegenerative diseases. CONCLUSION: Medicinal plants for anti-neurodegenerative diseases in West Africa have been documented with their neuropharmacological activities. Plant families such as Fabaceae, Solanaceae, Apocynaceae, Asteraceae, and Euphorbiaceae could be a major natural source for discovery of anti-neurodegenerative drugs, thus the metabolites from them should be given priority for neurological research. This review will provide clues for further investigations on the screening and development of anti-neurodegenerative natural products from West African medicinal plants.

Whole and fractionated human platelet lysate biomaterials-based biotherapy induces strong neuroprotection in experimental models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease of motor neurons leading to death within 3 years and without a curative treatment. Neurotrophic growth factors (NTFs) are pivotal for cell survival. A reason for the lack of patient efficacy with single recombinant NTF brain infusion is likely to be due to the synergistic neuroprotective action of multiple NTFs on a diverse set of signaling pathways. Fractionated (protein size <50, <30, <10, <3 kDa) heat-treated human platelet lysate (HHPL) preparations were adapted for use in brain tissue with the aim of demonstrating therapeutic value in ALS models and further elucidation of the mechanisms of action. In neuronal culture all fractions induced Akt-dependent neuroprotection as well as a strong anti-apoptotic and anti-ferroptotic action. In the <3 kDa fraction anti-ferroptotic properties were shown to be GPX4 dependent highlighting a role for other platelet elements associated with NTFs. In the SOD1G86R mouse model, lifespan was strongly increased by intracerebroventricular delivery of HHPL or by intranasal administration of <3 kDa fraction. Our results suggest that the platelet lysate biomaterials are neuroprotective in ALS. Further studies would now validate theragnostic biomarker on its antiferroptotic action, for further clinical development.

[Transcranial photobiomodulation in therapy of neurodegenerative diseases of the brain: theoretical background and clinical effectiveness]. / Transkranial'naya fotobiomodulyatsiya v terapii neirodegenerativnykh zabolevanii golovnogo mozga: teoreticheskie predposylki i klinicheskaya effektivnost'.

Transcranial photobiomodulation (tPBM) is a form of light therapy that uses monochromatic visible and infrared light from non-ionizing radiation sources (lasers, LEDs) placed on the scalp, forehead, or intranasally to project light directly to target areas of the brain. Accumulated experimental and clinical data indicate the safety and potential efficacy of tPBM in some central nervous system diseases.This article briefly reviews the general concepts of tPBM, the results of experimental and clinical studies on the efficacy of tPBM in Alzheimer's disease, Parkinson's disease, and brain stroke. The possible mechanisms of the tPBM therapeutic effect and the need to choose optimal exposure parameters are discussed. Although the evidence base regarding the efficacy of tPBM in neurodegenerative and vascular brain diseases is still insufficient, analysis of the published data justifies considering tPBM as a promising method of adjuvant therapy for some central nervous system diseases.

Hyperbaric Oxygen Treatment-From Mechanisms to Cognitive Improvement.

Hyperbaric oxygen treatment (HBOT)-the medical use of oxygen at environmental pressure greater than one atmosphere absolute-is a very effective therapy for several approved clinical situations, such as carbon monoxide intoxication, incurable diabetes or radiation-injury wounds, and smoke inhalation. In recent years, it has also been used to improve cognition, neuro-wellness, and quality of life following brain trauma and stroke. This opens new avenues for the elderly, including the treatment of neurological and neurodegenerative diseases and improvement of cognition and brain metabolism in cases of mild cognitive impairment. Alongside its integration into clinics, basic research studies have elucidated HBOT's mechanisms of action and its effects on cellular processes, transcription factors, mitochondrial function, oxidative stress, and inflammation. Therefore, HBOT is becoming a major player in 21st century research and clinical treatments. The following review will discuss the basic mechanisms of HBOT, and its effects on cellular processes, cognition, and brain disorders.

Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases.

Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life.

The possibilities of using the effects of ozone therapy in neurology.

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHODS: The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULTS: Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION: Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.

iPSCs: A Preclinical Drug Research Tool for Neurological Disorders.

The development and commercialization of new drugs is an articulated, lengthy, and very expensive process that proceeds through several steps, starting from target identification, screening new leading compounds for testing in preclinical studies, and subsequently in clinical trials to reach the final approval for therapeutic use. Preclinical studies are usually performed using both cell cultures and animal models, although they do not completely resume the complexity of human diseases, in particular neurodegenerative conditions. To this regard, stem cells represent a powerful tool in all steps of drug discovery. The recent advancement in induced Pluripotent Stem Cells (iPSCs) technology has opened the possibility to obtain patient-specific disease models for drug screening and development. Here, we report the use of iPSCs as a disease model for drug development in the contest of neurological disorders, including Alzheimer's (AD) and Parkinson's disease (PD), Amyotrophic lateral Sclerosis (ALS), and Fragile X syndrome (FRAX).

Glutathione peroxidase-1 and neuromodulation: Novel potentials of an old enzyme.

Glutathione peroxidase (GPx) acts in co-ordination with other signaling molecules to exert its own antioxidant role. We have demonstrated the protective effects of GPx,/GPx-1, a selenium-dependent enzyme, on various neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, cerebral ischemia, and convulsive disorders). In addition, we summarized the recent findings indicating that GPx-1 might play a role as a neuromodulator in neuropsychiatric conditions, such as, stress, bipolar disorder, schizophrenia, and drug intoxication. In this review, we attempted to highlight the mechanistic scenarios mediated by the GPx/GPx-1 gene in impacting these neurodegenerative and neuropsychiatric disorders, and hope to provide new insights on the therapeutic interventions against these disorders.

Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications.

Copper is one of the most abundant basic transition metals in the human body. It takes part in oxygen metabolism, collagen synthesis, and skin pigmentation, maintaining the integrity of blood vessels, as well as in iron homeostasis, antioxidant defense, and neurotransmitter synthesis. It may also be involved in cell signaling and may participate in modulation of membrane receptor-ligand interactions, control of kinase and related phosphatase functions, as well as many cellular pathways. Its role is also important in controlling gene expression in the nucleus. In the nervous system in particular, copper is involved in myelination, and by modulating synaptic activity as well as excitotoxic cell death and signaling cascades induced by neurotrophic factors, copper is important for various neuronal functions. Current data suggest that both excess copper levels and copper deficiency can be harmful, and careful homeostatic control is important. This knowledge opens up an important new area for potential therapeutic interventions based on copper supplementation or removal in neurodegenerative diseases including Wilson's disease (WD), Menkes disease (MD), Alzheimer's disease (AD), Parkinson's disease (PD), and others. However, much remains to be discovered, in particular, how to regulate copper homeostasis to prevent neurodegeneration, when to chelate copper, and when to supplement it.

Electroacupuncture Improves Motor Symptoms of Parkinson's Disease and Promotes Neuronal Autophagy Activity in Mouse Brain.

Autophagic defects are a hallmark of neurodegenerative disorders, such as Parkinson's disorder (PD). Enhancing autophagy to remove impaired mitochondria and toxic protein aggregation is an essential component of PD treatment. In particular, activation of autophagy confers neuroprotection in cellular and preclinical models of neurodegenerative diseases. In this study, we investigated the therapeutic mechanisms of electroacupuncture (EA) treatment in mice with established PD and evaluated the relationship between EA, autophagy, and different neurons in the mouse brain. We report that EA improves PD motor symptoms in mice and enhances (1) autophagy initiation (increased Beclin 1), (2) autophagosome biogenesis (increased Atg5, Atg7, Atg9A, Atg12, Atg16L, Atg3, and LC3-II), (3) autophagy flux/substrate degradation (decreased p62), and (4) mitophagy (increased PINK1 and DJ-1) in neurons of the substantia nigra, striatum, hippocampus, and cortex (affected brain areas of PD, Huntington disease, and Alzheimer's disease). EA enhances autophagy initiation, autophagosome biogenesis, mitophagy, and autophagy flux/substrate degradation in certain brain areas. Our findings are the first to show that EA regulates neuronal autophagy and suggest that this convenient, inexpensive treatment has exciting therapeutic potential in neurodegenerative disorders.

Implicit Motor Imagery and the Lateral Occipitotemporal Cortex: Hints for Tailoring Non-Invasive Brain Stimulation.

BACKGROUND: Recent evidence has converged in showing that the lateral occipitotemporal cortex is over-recruited during implicit motor imagery in elderly and in patients with neurodegenerative disorders, such as Parkinson's disease. These data suggest that when automatically imaging movements, individuals exploit neural resources in the visual areas to compensate for the decline in activating motor representations. Thus, the occipitotemporal cortex could represent a cortical target of non-invasive brain stimulation combined with cognitive training to enhance motor imagery performance. Here, we aimed at shedding light on the role of the left and right lateral occipitotemporal cortex in implicit motor imagery. METHODS: We applied online, high-frequency, repetitive transcranial magnetic stimulation (rTMS) over the left and right lateral occipitotemporal cortex while healthy right-handers judged the laterality of hand images. RESULTS: With respect to the sham condition, left hemisphere stimulation specifically reduced accuracy in judging the laterality of right-hand images. Instead, the hallmark of motor simulation, i.e., the biomechanical effect, was never influenced by rTMS. CONCLUSIONS: The lateral occipitotemporal cortex seems to be involved in mental representation of the dominant hand, at least in right-handers, but not in reactivating sensorimotor information during simulation. These findings provide useful hints for developing combined brain stimulation and behavioural trainings to improve motor imagery.

[Aceruloplasminemia, a rare condition not to be overlooked]. / L'acéruléoplasminémie héréditaire, une pathologie à ne pas méconnaître.

Aceruloplasminemia is a rare iron-overload disease that should be better known by physicians. It is an autosomal recessive disorder due to mutations in ceruloplasmin gene causing systemic iron overload, including cerebral and liver parenchyma. The impairment of ferroxidase ceruloplasmin activity leads to intracellular iron retention leading aceruloplasminemia symptoms. Neurologic manifestations include cognitive impairment, ataxia, extrapyramidal syndrome, abnormal movements, and psychiatric-like syndromes. Physicians should search for aceruloplasminemia in several situations with high ferritin levels: microcytic anaemia, diabetes mellitus, neurological and psychiatric disorders. Diagnosis approach is based on the study of transferrin saturation and hepatic iron content evaluated by magnetic resonance imaging of the liver. Ceruloplasmin dosage is required in case of low transferrin saturation and high hepatic iron content and genetic testing is mandatory in case of serum ceruloplasmin defect. Neurological manifestations occur in the sixties decade and leads to disability. Iron chelators are widely used. Despite their efficacy on systemic and cerebral iron overload, iron chelators tolerance is poor. Early initiation of iron chelation therapy might prevent or slowdown neurodegeneration, highlighting the need for an early diagnosis but their clinical efficacy remains uncertain.

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses.

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.