Modulation of Gut Microbiota Through Dietary Intervention in Neuroinflammation and Alzheimer's and Parkinson's Diseases.

PURPOSE OF REVIEW: The gut microbiota plays a crucial role in the pathogenesis of neuroinflammation and Alzheimer's and Parkinson's diseases. One of the main modulators of the gut microbiota is the diet, which directly influences host homeostasis and biological processes. Some dietary patterns can affect neurodegenerative diseases' progression through gut microbiota composition, gut permeability, and the synthesis and secretion of microbial-derived neurotrophic factors and neurotransmitters. This comprehensive review critically assesses existing studies investigating the impact of dietary interventions on the modulation of the microbiota in relation to neurodegenerative diseases and neuroinflammation. RECENT FINDINGS: There are limited studies on the effects of specific diets, such as the ketogenic diet, Mediterranean diet, vegetarian diet, and Western diet, on the progression of neuroinflammation and Alzheimer's and Parkinson's diseases through the gut-brain axis. The ketogenic diet displays promising potential in ameliorating the clinical trajectory of mild cognitive impairment and Alzheimer's disease. However, conflicting outcomes were observed among various studies, highlighting the need to consider diverse types of ketogenic diets and their respective effects on clinical outcomes and gut microbiota composition. Vegetarian and Mediterranean diets, known for their anti-inflammatory properties, can be effective against Parkinson's disease, which is related to inflammation in the gut environment. On the other hand, the westernization of dietary patterns was associated with reduced gut microbial diversity and metabolites, which ultimately contributed to the development of neuroinflammation and cognitive impairment. Various studies examining the impact of dietary interventions on the gut-brain axis with regard to neuroinflammation and Alzheimer's and Parkinson's diseases are thoroughly reviewed in this article. A strong mechanistic explanation is required to fully understand the complex interactions between various dietary patterns, gut microbiota, and microbial metabolites and the effects these interactions have on cognitive function and the progression of these diseases.

Effects of dietary supplements, foods, and dietary patterns in Parkinson's disease: meta-analysis and systematic review of randomized and crossover studies.

BACKGROUND: Diet significantly impacts Parkinson's disease (PD) with plausible biological hypotheses. Although the thesis has been explored in several human clinical trials, no current meta-analyses or reviews summarize the results. We examined the effect of intervention of dietary supplements, foods, and dietary patterns in treating PD. METHODS: We conducted a meta-analysis and systematic review of randomized and crossover studies published between 1989 and 26 June 2022, searching from PubMed, Embase, Medline, Scopus, Cochrane Library databases, and Chinese databases. Twenty-four studies were included in this review. RESULTS: The meta-analysis results show that dietary supplements intervention significantly increased the quantitative insulin sensitivity check index (QUICKI) [MD = 0.02, 95% CI (0.01, 0.02), p < 0.00001]. Dietary supplement intervention does not significantly affect the total Unified Parkinson Disease Rating Scale (UPDRS) score and six-min walk test (6MWT) distance. We did not find evidence that dietary supplements or food intervention may minimize the UPDRS III score. However, systematic review results indicated that the Mediterranean, low-fat, and ketogenic diets significantly reduced the total UPDRS score; low-protein diets meaningfully mitigated motor symptoms. CONCLUSIONS: This meta-analysis result displays that diet and diet supplements had a very modest but statistically significant impact on QUICKI but no effect on motor and non-motor symptoms in PD. The systematic review concludes that dietary patterns intervention may positively attenuate the overall symptoms of PD, including both motor and non-motor symptoms.

Dietary Interventions in Parkinson's Disease.

Several dietary patterns and nutritional supplements have been linked to the development, progression, and symptomatic treatment of Parkinson's disease (PD). Most of the evidence, at this point, is preliminary and based largely on observational studies. Interventional studies are scarce, so the evidence on effectiveness remains inconclusive. Dietary interventions could, analogous to exercise, potentially have a beneficial effect on disease symptoms as well as on the progression of the disease and should therefore be researched in high quality studies. Further work is also needed to study whether dietary interventions, when applied to an at-risk population, have any potential to postpone the onset of manifest PD. In this paper, we summarize all ongoing clinical trials on dietary interventions in PD. We found 10 ongoing studies, all aimed at a different intervention. These studies are mostly exploratory in nature or represent phase I or phase II trials focusing on safety, biological responses, and symptomatic effects. Taken together, we conclude that research on dietary interventions in persons with PD is still in its early days. The results of the various ongoing trials are expected to generate new hypotheses and will help to shape the agenda for future research on this important topic.

Nutritional Ketosis in Parkinson's Disease - a Review of Remaining Questions and Insights.

Nutritional ketosis has promise for treating Parkinson's disease. Three previous studies explored the use of a ketogenic diet in cohorts with Parkinson's disease, and, while not conclusive, the data suggest non-motor symptom benefit. Before the ketogenic diet can be considered as a therapeutic option, it is important to establish with greater certainty that there is a reliable symptomatic benefit: which symptoms or groups of symptoms are impacted (if non-motor symptoms, which ones, and by which mechanism), what timescale is needed to obtain benefit, and how large an effect size can be achieved? To accomplish this, further investigation into the disease mechanisms based on pre-clinical data and hints from the clinical outcomes to date is useful to understand target engagement and gauge which mechanism could lead to a testable hypothesis. We review research pertaining to ketogenic diet, exogenous ketones, fasting, clinical studies, and theoretical review papers regarding therapeutic mechanisms from direct ketone body signaling and indirect metabolic effects. Through discussion of these findings and consideration of whether the ketogenic diet can be regarded as therapeutically useful for adjunctive therapy for Parkinson's disease, we identify remaining questions for the clinician to consider prior to recommending this diet.

Effect of dietary vitamins C and E on the risk of Parkinson's disease: A meta-analysis.

BACKGROUND & AIMS: A neuroprotective effect of dietary vitamins C and E on Parkinson's disease (PD) has been suggested, however, several human studies have reported controversial results. Therefore, we conducted a meta-analysis on the effect of vitamins C and E on the risk of Parkinson's disease. METHODS: A comprehensive literature search was conducted using the PubMed, EMBASE, Cochrane Library, and SCOPUS databases for studies published up to January 23, 2021. We included studies that reported (1) intake of vitamins C and E using validated methods; (2) assessment of odds ratio (OR), relative risk (RR), or hazard ratio (HR); and (3) patients with PD identified by a neurologist, hospital records, or death certificates. The Comprehensive Meta-Analysis Software 2 program was used for statistical analyses of the pooled data. RESULTS: A total of 12 studies (four prospective cohort and eight case-control studies) were included in our meta-analysis. No significant risk reduction was observed in the high vitamin C intake group compared to low intake group. On the other hand, the high vitamin E intake group showed a significantly lower risk of development of PD than the low intake group (pooled OR = 0.799. 95% CI = 0.721 to 0.885). CONCLUSIONS: We conclude that vitamin E might have a protective effect against PD, while vitamin C does not seem to have such an effect. However, the exact mechanism of the transport and regulation of vitamin E in the CNS remains elusive, and further studies would be necessary in this field.

Ketogenic diet and cognition in neurological diseases: a systematic review.

CONTEXT: In recent years, the ketogenic diet has gained special relevance as a possible therapeutic alternative to some neurological and chronic diseases. OBJECTIVE: The aim of this systematic review was to answer the following question: Does a ketogenic diet improve cognitive skills in patients with Alzheimer's disease, Parkinson's disease, refractory epilepsy, and type 1 glucose deficiency syndrome? To define the research question, the PICOS criteria were used, following the guidelines of the PRISMA method. DATA SOURCES: Medline/PubMed, Elsevier Science Direct, Dialnet, EBSCOhost, Mediagraphic, Sage Journals, ProQuest, and Wiley Online Library databases were used. DATA EXTRACTION: After applying inclusion and exclusion criteria in accordance with the PRISMA method, a total of 63 entries published between 2004 and 2019 were used. DATA ANALYSIS: The records extracted were analyzed from a qualitative approach, so no statistical analysis was carried out. CONCLUSION: Although scientific literature on the subject is scarce and there has tended to be a lack of scientific rigor, the studies reviewed confirmed the effectiveness of this diet in improving the cognitive symptomatology of the aforementioned diseases.

Effect of ketogenic diet versus regular diet on voice quality of patients with Parkinson's disease.

Diets that have effects on health problems can vary in their composition. Whilst following a regular diet (RD) a person typically consumes about 30% of calories from fat. Ketogenic diet (KD) is a form of diet whereby a person consumes as much as 90% of calories from fat. KD has been trialed as a treatment for neurological diseases and obesity. Parkinson's disease (PD) is a neurologic disease that impacts the quality of voice. Voice Handicap Index (VHI) is a test that gives information to clinical and physiological assessment about voice. We assessed the impact of KD and RD on voice quality (VQ). Seventy-four patients with PD who reported a voice disorder related to their disease were randomly assigned to the KD or RD groups. We investigated the VHI change of subjects before and 3 months after diet. Sixty-eight PD patients completed the study. Baseline VHI values did not differ significantly between groups. All mean VHI parameters improved in KD group (p˂ 0.001). Currently there are different therapies that address speech and voice disorders in patients with PD. As such KD may be an alternative therapy to improve VQ of patients with PD. A larger sample size is necessary to determine the role and pathophysiology of KD on VQ of PD patients.

Evaluating the Effects of Grain of Isogenic Wheat Lines Differing in the Content of Anthocyanins in Mouse Models of Neurodegenerative Disorders.

Functional foods enriched with plant polyphenols and anthocyanins in particular attract special attention due to multiple beneficial bioactive properties of the latter. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Alzheimer's disease induced by amyloid-beta (Aß) and a transgenic mouse model of Parkinson's disease (PD) with overexpression of human alpha-synuclein. The mice were kept at a diet that consisted of the wheat grain of near isogenic lines differing in anthocyanin content for five-six months. The anthocyanin-rich diet was safe and possessed positive effects on cognitive function. Anthocyanins prevented deficits in working memory induced by Aß or a long-term grain mono-diet; they partially reversed episodic memory alterations. Both types of grain diets prolonged memory extinction and rescued its facilitation in the PD model. The dynamics of the extinction in the group fed with the anthocyanin-rich wheat was closer to that in a group of wild-type mice given standard chow. The anthocyanin-rich diet reduced alpha-synuclein accumulation and modulated microglial response in the brain of the transgenic mice including the elevated expression of arginase1 that marks M2 microglia. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition at the early stages of neurodegenerative disorders.

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases.

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

The Pathology of Parkinson's Disease and Potential Benefit of Dietary Polyphenols.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a loss of dopaminergic neurons, leading to bradykinesia, rigidity, tremor at rest, and postural instability, as well as non-motor symptoms such as olfactory impairment, pain, autonomic dysfunction, impaired sleep, fatigue, and behavioral changes. The pathogenesis of PD is believed to involve oxidative stress, disruption to mitochondria, alterations to the protein α-synuclein, and neuroinflammatory processes. There is currently no cure for the disease. Polyphenols are secondary metabolites of plants, which have shown benefit in several experimental models of PD. Intake of polyphenols through diet is also associated with lower PD risk in humans. In this review, we provide an overview of the pathology of PD and the data supporting the potential neuroprotective capacity of increased polyphenols in the diet. Evidence suggests that the intake of dietary polyphenols may inhibit neurodegeneration and the progression of PD. Polyphenols appear to have a positive effect on the gut microbiome, which may decrease inflammation that contributes to the disease. Therefore, a diet rich in polyphenols may decrease the symptoms and increase quality of life in PD patients.

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.

Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.

Dietary Amino Acids Impact LRRK2-Induced Neurodegeneration in Parkinson's Disease Models.

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of Parkinson's disease (PD) and results in age-related dopamine neuron loss and locomotor dysfunction in Drosophila melanogaster through an aberrant increase in bulk neuronal protein synthesis. Under nonpathologic conditions, protein synthesis is tightly controlled by metabolic regulation. Whether nutritional and metabolic influences on protein synthesis can modulate the pathogenic effect of LRRK2 on protein synthesis and thereby impact neuronal loss is a key unresolved question. Here, we show that LRRK2 G2019S-induced neurodegeneration is critically dependent on dietary amino acid content in Drosophila studies with both sexes. Low dietary amino acid concentration prevents aberrant protein synthesis and blocks LRRK2 G2019S-mediated neurodegeneration in Drosophila and rat primary neurons. Unexpectedly, a moderately high-amino acid diet also blocks dopamine neuron loss and motor deficits in Drosophila through a separate mechanism involving stress-responsive activation of 5'-AMP-activated protein kinase (AMPK) and neuroprotective induction of autophagy, implicating the importance of protein homeostasis to neuronal viability. At the highest amino acid diet of the range tested, PD-related neurodegeneration occurs in an age-related manner, but is also observed in control strains, suggesting that it is independent of mutant LRRK2 expression. We propose that dietary influences on protein synthesis and autophagy are critical determinants of LRRK2 neurodegeneration, opening up possibilities for future therapeutic intervention.SIGNIFICANCE STATEMENT Parkinson's disease (PD) prevalence is projected to rise as populations continue to age, yet there are no current therapeutic approaches that delay or stop disease progression. A broad role for leucine-rich repeat kinase 2 (LRRK2) mutations in familial and idiopathic PD has emerged. Here, we show that dietary amino acids are important determinants of neurodegeneration in a Drosophila model of LRRK2 PD. Restricting all amino acids effectively suppresses dopaminergic neuron loss and locomotor deficits and is associated with reduced protein synthesis, while moderately high amino acids similarly attenuate these PD-related phenotypes through a stress-responsive induction of 5'-AMP-activated protein kinase and autophagy. These studies suggest that diet plays an important role in the development of PD-related phenotypes linked to LRRK2.

Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson's Models.

Parkinson's disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its "natural" environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.

The effect of the Mediterranean diet on cognitive function in patients with Parkinson's disease: A randomized clinical controlled trial.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is proposed that adherence to the Mediterranean diet might have a beneficial effect on the prevention and treatment of PD and its complications. Thus, the aim of this study was to investigate the effects of the Mediterranean diet on cognitive function in patients with PD. DESIGN: The study was a single-center, randomized clinical trial. Eighty patients with idiopathic PD were randomly allocated to the Mediterranean diet (n = 40) or control (n = 40) group. Patients in the intervention group received an individualized dietary plan based on Mediterranean diet for 10 weeks. The Persian version of Montreal Cognitive Assessment (MoCA) test was used to assess the cognitive function at baseline and the end of the study. RESULTS: Thirty-five PD patients with a mean age of 59.3 ±â€¯8.3 and 35 patients with a mean age of 58.6 ±â€¯9.3 finished the study in intervention and control groups, respectively. After the intervention, the mean score of the dimensions of executive function, language, attention, concentration, and active memory and the total score of cognitive assessment significantly increased in the intervention compared with the control group (p < 0.05, for all). Nevertheless, the mean of the other scores including spatial-visual ability, memory learning task, and navigation versus time and place did not significantly change in both intervention and control groups. CONCLUSIONS: The findings of this study showed that adherence to the Mediterranean diet remarkably increased the dimensions of executive function, language, attention, concentration, and active memory and finally the total score of cognitive assessment in PD patients.

Healthy Effects of Plant Polyphenols: Molecular Mechanisms.

The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer's and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

Faecal Transplantation, Pro- and Prebiotics in Parkinson's Disease; Hope or Hype?

Faecal microbiome transplantation (FMT) is an attractive technique, because the administration is relatively simple and in general has a mild adverse effect pattern. Moreover, FMT consists of a broad mixture, which could be beneficial, because at this moment it is not known what type of changes in the microbiome are needed. However, except from a few cases no clinical data in Parkinson's disease (PD) is available yet. There is some indication that FMT might be beneficial in severe constipated PD patients, but the clinical data to support this are very scarce. So, actually there are no good data in the public domain to support FMT at this moment in PD patients. FMT at this moment is a black box with too many unanswered questions, also with respect to safety concerns. Only the administration of species of Lactobacillus and Bifidobacterium over a time period of four to twelve weeks has repeatedly proven to be effective in treating constipation in PD. Also, no solid clinical data are available about the possible effects of probiotic treatment on motor symptoms or progression of PD. Therefore, also probiotic treatments in PD should wait until better clinical data become available, in order to select the right target populations and to have good estimates of the clinical effects to be expected.

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease.

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.

Lessons learned from recent clinical trials of ketogenic diet therapies in adults.

PURPOSE OF REVIEW: Although ketogenic diet therapies (KDTs) were first developed as a treatment for patients with epilepsy, their potential efficacy for a broader number of neurologic and nonneurologic disorders and conditions has been explored over the last 10-20 years. The most recent clinical trials of KDTs in adults have highlighted common methodological aspects that can either facilitate or thwart appropriate risk/benefit analyses, comparisons across studies, and reproducibility of findings in future studies. RECENT FINDINGS: Recent evidence suggests that KDTs not only improve seizure control, but also improve other neurologic conditions, including nonmotor Parkinson's disease symptoms. Therapies targeting nutritional ketosis without comprehensive diet modification improve cognition and cerebral blood flow in Alzheimer's disease patients. KDTs lower hemoglobin A1c levels and diabetes medication use in patients with Type 2 diabetes and mixed results have been observed when used for performance enhancement in athletes and healthy volunteers. SUMMARY: Clinical studies of KDTs show promise for a variety of clinical indications. Future studies should factor in high potential participant attrition rates and utilize consistent and standard reporting of diet type(s), compliance measures, and side-effects to enable the reproducibility and generalizability of study outcomes.

Probiotics for Parkinson's Disease.

Parkinson's disease (PD) is a complex neurological disorder classically characterized by impairments in motor system function associated with loss of dopaminergic neurons in the substantia nigra. After almost 200 years since the first description of PD by James Parkinson, unraveling the complexity of PD continues to evolve. It is now recognized that an interplay between genetic and environmental factors influences a diverse range of cellular processes, reflecting on other clinical features including non-motor symptoms. This has consequently highlighted the extensive value of early clinical diagnosis to reduce difficulties of later stage management of PD. Advancement in understanding of PD has made remarkable progress in introducing new tools and strategies such as stem cell therapy and deep brain stimulation. A link between alterations in gut microbiota and PD has also opened a new line. Evidence exists of a bidirectional pathway between the gastrointestinal tract and the central nervous system. Probiotics, prebiotics and synbiotics are being examined that might influence gut-brain axis by altering gut microbiota composition, enteric nervous system, and CNS. This review provides status on use of probiotics for PD. Limitations and future directions will also be addressed to promote further research considering use of probiotics for PD.

Prioritized brain selenium retention and selenoprotein expression: Nutritional insights into Parkinson's disease.

Selenium (Se), an essential trace mineral, confers its physiological functions mainly through selenoproteins, most of which are oxidoreductases. Results from animal, epidemiological, and human genetic studies link Parkinson's disease to Se and certain selenoproteins. Parkinson's disease is characterized by multiple motor and non-motor symptoms that are difficult to diagnose at early stages of the pathogenesis. While irreversible, degenerative and age-related, the onset of Parkinson's disease may be delayed through proper dietary and environmental controls. One particular attribute of Se biology is that brain has the highest priority to receive and retain this nutrient even in Se deficiency. Thus, brain Se deficiency is rare; however, a strong body of recent evidence implicates selenoprotein dysfunction in Parkinson's disease. Direct and indirect evidence from mouse models implicate selenoprotein T, glutathione peroxidase 1, selenoprotein P and glutathione peroxidase 4 in counteracting Parkinson's disease through Se transportation to the brain and reduced oxidative stress. It is of future interest to further characterize the full selenoproteomes in various types of brain cells and elucidate the mechanism of their actions in Parkinson's disease.